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Home / Equine Research Bank / Equine Vet J / Pattern recognition receptors in equine endotoxaemia and sep...
Equine veterinary journal2012; 44(4); 490-498; doi: 10.1111/j.2042-3306.2012.00574.x

Pattern recognition receptors in equine endotoxaemia and sepsis.

Abstract: Pattern recognition receptors (PRRs) on host cells detect pathogens to activate innate immunity which, in turn, initiates inflammatory and adaptive immune responses. Successful activation of PRRs is, therefore, critical to controlling infections and driving pathogen-specific adaptive immunity, but overactivity of PRRs causes systemic inflammation, which is detrimental to the host. Here we review the PRR literature as it relates to horses and speculate on the role PRRs may play in sepsis and endotoxaemia.
© 2012 EVJ Ltd.
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Publication Date: 2012-05-20 PubMed ID: 22607193PubMed Central: PMC7199481DOI: 10.1111/j.2042-3306.2012.00574.xGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on the role of Pattern Recognition Receptors (PRRs) in equine endotoxemia and sepsis. An overactive PRR response can lead to systemic inflammation, which can be harmful.

Pattern Recognition Receptors in Innate Immunity

  • The primary function of Pattern Recognition Receptors (PRRs) is to detect dangerous pathogens in the body. This detection activates the body’s innate immunity, and, consequently, triggers inflammatory and adaptive immune responses.
  • Therefore, these receptors play a critical role in controlling infections and promoting pathogen-specific adaptive immune responses in horses. Without successful activation of PRRs, the immune system may not respond adequately to infections.

Detrimental Effects of Overactive PRRs

  • While the activation of PRRs is crucial in initiating the appropriate immune responses, this process needs to be properly regulated. Overactive PRRs can cause systemic inflammation, which can be harmful to the host.
  • Systemic inflammation refers to the body’s overactive immune response that harms its own tissue. It can lead to organ failure and can be potentially fatal if left unchecked.

PRRs and Sepsis in Horses

  • Sepsis is a life-threatening condition triggered by the body’s extreme response to an infection. When it comes to equine health, understanding the role of PRRs in sepsis could pave the way for better management of the condition.
  • There’s a possibility that an overactive PRR response may be a factor contributing to the onset of sepsis in horses. This hypothesis is yet to be fully explored with further research needed.

PRRs and Endotoxemia in Horses

  • Endotoxemia in horses occurs when endotoxins, generally found in the outer membrane of gram-negative bacteria, enter the bloodstream causing an excessive immune response. This turns these bacteria into a significant threat to equine health.
  • The role of PRRs in such scenarios is particularly interesting. There is speculation that PRRs can potentially contribute to endotoxemia in horses due to their ability to enhance the body’s immune response to the endotoxins. However, this relationship needs further investigation.

Cite This Article

APA
Werners AH, Bryant CE. (2012). Pattern recognition receptors in equine endotoxaemia and sepsis. Equine Vet J, 44(4), 490-498. https://doi.org/10.1111/j.2042-3306.2012.00574.x

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 44
Issue: 4
Pages: 490-498

Researcher Affiliations

Werners, A H
  • Anatomy, Physiology and Pharmacology Academic Programme, School of Veterinary Medicine, St George's University, True Blue, Grenada, West Indies.
Bryant, C E

    MeSH Terms

    • Animals
    • Endotoxemia / metabolism
    • Endotoxemia / veterinary
    • Horse Diseases / metabolism
    • Horses
    • Receptors, Pattern Recognition / metabolism
    • Sepsis / metabolism

    Grant Funding

    • BB/H003916/1 / Biotechnology and Biological Sciences Research Council

    References

    This article includes 184 references
    1. Roy MF. Sepsis in adults and foals. Vet. Clin. N. Am.: Equine Pract. 20, 41‐61.
      pubmed: 15062458
    2. Lever A, Mackenzie I. Sepsis: definition, epidemiology, and diagnosis. BMJ 335, 879‐883.
      pmc: PMC2043413pubmed: 17962288
    3. Cohen J, Abraham E. Microbiologic findings and correlations with serum tumor necrosis factor‐α in patients with severe sepsis and septic shock. J. Infect. Dis. 180, 116‐121.
      pubmed: 10353869
    4. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N. Engl. J. Med. 348, 1546‐1554.
      pubmed: 12700374
    5. Myhre AE, Aasen AO, Thiemermann C, Wang JE. Peptidoglycan – an endotoxin in its own right?. Shock 25, 227‐235.
      pubmed: 16552353
    6. Sanchez LC. Equine neonatal sepsis. Vet. Clin. N. Am.: Equine Pract. 21, 273‐293.
      pubmed: 16051050
    7. Pusterla N, Mapes S, Byrne BA, Magdesian KG. Detection of bloodstream infection in neonatal foals with suspected sepsis using real‐time PCR. Vet. Rec. 165, 114‐117.
      pubmed: 19633325
    8. Russell CM, Axon JE, Blishen A, Begg AP. Blood culture isolates and antimicrobial sensitivities from 427 critically ill neonatal foals. Aust. Vet. J. 86, 266‐271.
      pubmed: 18616477
    9. Corley KTT, Pearce G, Magdesian KG, Wilson WD. Bacteraemia in neonatal foals: clinicopathological differences between Gram‐positive and Gram‐negative infections, and single organism and mixed infections. Equine Vet. J. 39, 84‐89.
      pubmed: 17228602
    10. Johns I, Tennent‐Brown B, Schaer BD, Southwood L, Boston R, Wilkins P. Blood culture status in mature horses with diarrhoea: a possible association with survival. Equine Vet. J. 41, 160‐164.
      pubmed: 19418745
    11. Hollis AR, Wilkins PA, Palmer JE, Boston RC. Bacteremia in equine neonatal diarrhea: a retrospective study (1990–2007). J. Vet. Intern. Med. 22, 1203‐1209.
      pubmed: 18638014
    12. Monie TP, Bryant CE, Gay NJ. Activating immunity: lessons from the TLRs and NLRs. Trends Biochem. Sci. 34, 553‐561.
      pubmed: 19818630
    13. O'Neill L, Bryant C, Doyle S. Therapeutic targeting of Toll‐like receptors for infectious and inflammatory diseases and cancer. Pharmacol. Rev. 61, 177‐197.
      pmc: PMC2846156pubmed: 19474110
    14. Gay NJ, Gangloff M. Structure and function of Toll receptors and their ligands. Annu. Rev. Biochem. 76, 141‐165.
      pubmed: 17362201
    15. Bryant CE, Spring DR, Gangloff M, Gay NJ. The molecular basis of the host response to lipopolysaccharide. Nat. Rev. Microbiol. 8, 8‐14.
      pubmed: 19946286
    16. Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, Lee H, Lee JO. Crystal structure of the TLR1‐TLR2 heterodimer induced by binding of a tri‐acylated lipopeptide. Cell 130, 1071‐1082.
      pubmed: 17889651
    17. Poltorak A, He X, Smirnova I, Liu MY, Huffel CV, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi‐Castagnoli P, Layton B, Beutler B. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085‐2088.
      pubmed: 9851930
    18. Lohmann KL, Vandenplas ML, Barton MH, Bryant CE, Moore JN. The equine TLR4/MD‐2 complex mediates recognition of lipopolysaccharide from Rhodobacter sphaeroides as an agonist. J. Endotoxin Res. 13, 235‐242.
      pubmed: 17956942
    19. Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO. The structural basis of lipopolysaccharide recognition by the TLR4–MD‐2 complex. Nature 458, 1191‐1195.
      pubmed: 19252480
    20. Tobias PS, Soldau K, Ulevitch RJ. Isolation of a lipopolysaccharide‐binding acute phase reactant from rabbit serum. J. Exp. Med. 164, 777‐793.
      pmc: PMC2188379pubmed: 2427635
    21. Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249, 1431‐1433.
      pubmed: 1698311
    22. Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M. MD‐2, a molecule that confers lipopolysaccharide responsiveness on Toll‐like receptor 4. J. Exp. Med. 189, 1777‐1782.
      pmc: PMC2193086pubmed: 10359581
    23. Kovach NL, Yee E, Munford RS, Raetz CR, Harlan JM. Lipid IVA inhibits synthesis and release of tumor necrosis factor induced by lipopolysaccharide in human whole blood ex vivo. J. Exp. Med. 172, 77‐84.
      pmc: PMC2188140pubmed: 2193101
    24. Walsh C, Gangloff M, Monie T, Smyth T, Wei B, McKinley TJ, Maskell D, Gay N, Bryant C. Elucidation of the MD‐2/TLR4 interface required for signaling by lipid IVa. J. Immunol. 181, 1245‐1254.
      pubmed: 18606678
    25. Vogel SN, Madonna GS, Wahl LM, Rick PD. In vitro stimulation of C3H/HeJ spleen cells and macrophages by a lipid A precursor molecule derived from Salmonella typhimurium. J. Immunol. 132, 347‐353.
      pubmed: 6361124
    26. Golenbock DT, Hampton RY, Qureshi N, Takayama K, Raetz CR. Lipid A‐like molecules that antagonize the effects of endotoxins on human monocytes. J. Biol. Chem. 266, 19490‐19498.
      pubmed: 1918061
    27. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 124, 783‐801.
      pubmed: 16497588
    28. Senior JM, Proudman CJ, Leuwer M, Carter SD. Plasma endotoxin in horses presented to an equine referral hospital: correlation to selected clinical parameters and outcomes. Equine Vet. J. 43, 585‐591.
      pubmed: 21496089
    29. Steverink PJ, Sturk A, Rutten VP, Wagenaar‐Hilbers JP, Klein WR, van der Velden MA, Nemeth F. Endotoxin, interleukin‐6 and tumor necrosis factor concentrations in equine acute abdominal disease: relation to clinical outcome. J. Endotoxin Res. 2, 289‐299.
    30. Hunt JM, Edwards GB, Clarke KW. Incidence, diagnosis and treatment of postoperative complications in colic cases. Equine Vet. J. 18, 264‐270.
      pubmed: 3758002
    31. Bailey SR, Adair HS, Reinemeyer CR, Morgan SJ, Brooks AC, Longhofer SL, Elliott J. Plasma concentrations of endotoxin and platelet activation in the developmental stage of oligofructose‐induced laminitis. Vet. Immunol. Immunopathol. 129, 167‐173.
      pubmed: 19091426
    32. Barton MH, Williamson L, Jacks S, Norton N. Effects on plasma endotoxin and eicosanoid concentrations and serum cytokine activities in horses competing in a 48‐, 83‐, or 159‐km endurance ride under similar terrain and weather conditions. Am. J. Vet. Res. 64, 754‐761.
      pubmed: 12828262
    33. Barton MH, Morris DD, Norton N, Prasse KW. Hemostatic and fibrinolytic indices in neonatal foals with presumed septicemia. J. Vet. Intern. Med. 12, 26‐35.
      pubmed: 9503357
    34. Peek SF, Semrad S, McGuirk SM, Riseberg A, Ann Slack J, Marques F, Coombs D, Lien L, Keuler N, Darien BJ. Prognostic value of clinicopathologic variables obtained at admission and effect of antiendotoxin plasma on survival in septic and critically ill foals. J. Vet. Intern. Med. 20, 569‐574.
      pubmed: 16734091
    35. Pirie RS, Collie DDS, Dixon PM, McGorum BC. Inhaled endotoxin and organic dust particulates have synergistic proinflammatory effects in equine heaves (organic dust‐induced asthma). Clin. Exp. Allergy 33, 676‐683.
      pubmed: 12752598
    36. Simonen‐Jokinen T, Pirie RS, McGorum B, Maisi P. Dose responses to inhalation of endotoxin, hay dust suspension and Aspergillus fumigatus extract in horses as measured by levels and activation of matrix metalloproteinase‐9. Equine Vet. J. 37, 155‐160.
      pubmed: 15779629
    37. Berndt A, Derksen FJ, Venta PJ, Ewart S, Yuzbasiyan‐Gurkan V, Robinson NE. Elevated amount of Toll‐like receptor 4 mRNA in bronchial epithelial cells is associated with airway inflammation in horses with recurrent airway obstruction. Am. J. Physiol. Lung Cell. Mol. Physiol. 292, L936‐L943.
      pubmed: 17158595
    38. Singh Suri S, Janardhan KS, Parbhakar O, Caldwell S, Appleyard G, Singh B. Expression of toll‐like receptor 4 and 2 in horse lungs. Vet. Res. 37, 541‐551.
      pubmed: 16641015
    39. Kang JY, Nan X, Jin MS, Youn SJ, Ryu YH, Mah S, Han SH, Lee H, Paik SG, Lee JO. Recognition of lipopeptide patterns by Toll‐like receptor 2‐Toll‐like receptor 6 heterodimer. Immunity 31, 873‐884.
      pubmed: 19931471
    40. Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, Takeda K, Akira S. Differential roles of TLR2 and TLR4 in recognition of gram‐negative and gram‐positive bacterial cell wall components. Immunity 11, 443‐451.
      pubmed: 10549626
    41. Lorenz E, Mira JP, Cornish KL, Arbour NC, Schwartz DA. A novel polymorphism in the toll‐like receptor 2 gene and its potential association with staphylococcal infection. Infect. Immun. 68, 6398‐6401.
      pmc: PMC97725pubmed: 11035751
    42. Fan J, Frey RS, Malik AB. TLR4 signaling induces TLR2 expression in endothelial cells via neutrophil NADPH oxidase. J. Clin. Invest. 112, 1234‐1243.
      pmc: PMC213490pubmed: 14561708
    43. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A. The innate immune response to bacterial flagellin is mediated by Toll‐like receptor 5. Nature 410, 1099‐1103.
      pubmed: 11323673
    44. Van Asten FJ, Hendriks HG, Koninkx JF, Van der Zeijst BA, Gaastra W. Inactivation of the flagellin gene of Salmonella enterica serotype enteritidis strongly reduces invasion into differentiated Caco‐2 cells. FEMS Microbiol. Lett. 185, 175‐179.
      pubmed: 10754244
    45. Feary DJ, Hassel DM. Enteritis and colitis in horses. Vet. Clin. N. Am.: Equine Pract. 22, 437‐479, ix.
      pubmed: 16882483
    46. Bell JK, Mullen GE, Leifer CA, Mazzoni A, Davies DR, Segal DM. Leucine‐rich repeats and pathogen recognition in Toll‐like receptors. Trends Immunol. 24, 528‐533.
      pubmed: 14552836
    47. Andersen‐Nissen E, Smith KD, Strobe KL, Barrett SL, Cookson BT, Logan SM, Aderem A. Evasion of Toll‐like receptor 5 by flagellated bacteria. Proc. Natl. Acad. Sci. U.S.A. 102, 9247‐9252.
      pmc: PMC1166605pubmed: 15956202
    48. Smith KD, Andersen‐Nissen E, Hayashi F, Strobe K, Bergman MA, Barrett SL, Cookson BT, Aderem A. Toll‐like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nat. Immunol. 4, 1247‐1253.
      pubmed: 14625549
    49. Applequist SE, Wallin RP, Ljunggren HG. Variable expression of Toll‐like receptor in murine innate and adaptive immune cell lines. Int. Immunol. 14, 1065‐1074.
      pubmed: 12202403
    50. Hornung V, Rothenfusser S, Britsch S, Krug A, Jahrsdörfer B, Giese T, Endres S, Hartmann G. Quantitative expression of toll‐like receptor 1–10 mRNA in cellular subsets of human peripheral blood mononuclear cells and sensitivity to CpG oligodeoxynucleotides. J. Immunol. 168, 4531‐4537.
      pubmed: 11970999
    51. Keestra AM, de Zoete MR, van Aubel RA, van Putten JP. Functional characterization of chicken TLR5 reveals species‐specific recognition of flagellin. Mol. Immunol. 45, 1298‐1307.
      pubmed: 17964652
    52. Kwon S, Gewirtz AT, Hurley DJ, Robertson TP, Moore JN, Vandenplas ML. Disparities in TLR5 expression and responsiveness to flagellin in equine neutrophils and mononuclear phagocytes. J. Immunol. 186, 6263‐6270.
      pubmed: 21518971
    53. Lun SW, Wong CK, Ko FW, Hui DS, Lam CW. Expression and functional analysis of toll‐like receptors of peripheral blood cells in asthmatic patients: implication for immunopathological mechanism in asthma. J. Clin. Immunol. 29, 330‐342.
      pubmed: 19067129
    54. Liaudet L, Deb A, Pacher P, Mabley JG, Murthy KG, Salzman AL, Szabo C. The flagellin‐TLR5 axis: therapeutic opportunities. Drug News Perspect. 15, 397‐409.
      pubmed: 12677175
    55. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S. A Toll‐like receptor recognizes bacterial DNA. Nature 408, 740‐745.
      pubmed: 11130078
    56. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 392, 245‐252.
      pubmed: 9521319
    57. Chen J, Nag S, Vidi PA, Irudayaraj J. Single molecule in vivo analysis of Toll‐like receptor 9 and CpG DNA interaction. PLoS One 6, e17991.
      pmc: PMC3070698pubmed: 21483736
    58. Ewald SE, Engel A, Lee J, Wang M, Bogyo M, Barton GM. Nucleic acid recognition by Toll‐like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. J. Exp. Med. 208, 643‐651.
      pmc: PMC3135342pubmed: 21402738
    59. Avalos AM, Ploegh HL. Competition by inhibitory oligonucleotides prevents binding of CpG to C‐terminal TLR9. Eur. J. Immunol. 41, 2820‐2827.
      pmc: PMC3746339pubmed: 21766476
    60. Chuang TH, Ulevitch RJ. Cloning and characterization of a sub‐family of human toll‐like receptors: hTLR7, hTLR8 and hTLR9. Eur. Cytokine Netw. 11, 372‐378.
      pubmed: 11022120
    61. Franch R, Cardazzo B, Antonello J, Castagnaro M, Patarnello T, Bargelloni L. Full‐length sequence and expression analysis of Toll‐like receptor 9 in the gilthead seabream (Sparus aurata L.). Gene 378, 42‐51.
      pubmed: 16797882
    62. Yao CL, Kong P, Wang ZY, Ji PF, Cai MY, Liu XD, Han XZ. Cloning and expression analysis of two alternative splicing toll‐like receptor 9 isoforms A and B in large yellow croaker, Pseudosciaena crocea. Fish Shellfish Immunol. 25, 648‐656.
      pubmed: 18824108
    63. McKelvey KJ, Highton J, Hessian PA. Cell‐specific expression of TLR9 isoforms in inflammation. J. Autoimmun. 36, 76‐86.
      pubmed: 21115235
    64. Schneberger D, Caldwell S, Suri SS, Singh B. Expression of toll‐like receptor 9 in horse lungs. Anat. Rec. (Hoboken) 292, 1068‐1077.
      pubmed: 19548205
    65. Zhang YW, Davis EG, Blecha F, Wilkerson MJ. Molecular cloning and characterization of equine Toll‐like receptor 9. Vet. Immunol. Immunopathol. 124, 209‐219.
      pubmed: 18462806
    66. Gornik K, Moore P, Figueiredo M. Expression of Toll‐like receptors 2, 3, 4, 6, 9, and MD‐2 in the normal equine cornea, limbus, and conjunctiva. Vet. Ophthalmol. 14, 80‐85.
      pubmed: 21366822
    67. Liu M, Liu T, Bordin A, Nerren J, Cohen N. Activation of foal neutrophils at different ages by CpG oligodeoxynucleotides and Rhodococcus equi. Cytokine 48, 280‐289.
      pubmed: 19819162
    68. Flaminio MJB, Borges AS, Nydam DV, Horohov DW, Hecker R, Matychak MB. The effect of CpG‐ODN on antigen presenting cells of the foal. J. Immune Based Ther. Vaccines 5, 1.
      pmc: PMC1797044pubmed: 17254326
    69. Rietdijk ST, Burwell T, Bertin J, Coyle AJ. Sensing intracellular pathogens – NOD‐like receptors. Curr. Opin. Pharmacol. 8, 261‐266.
      pubmed: 18487086
    70. Horvath GL, Schrum JE, De Nardo CM, Latz E. Intracellular sensing of microbes and danger signals by the inflammasomes. Immunol. Rev. 243, 119‐135.
      pmc: PMC3893570pubmed: 21884172
    71. Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL‐β. Mol. Cell 10, 417‐426.
      pubmed: 12191486
    72. Girardin SE, Boneca IG, Carneiro LA, Antignac A, Jéhanno M, Viala J, Tedin K, Taha MK, Labigne A, Zähringer U, Coyle AJ, DiStefano PS, Bertin J, Sansonetti PJ, Philpott DJ. Nod1 detects a unique muropeptide from gram‐negative bacterial peptidoglycan. Science 300, 1584‐1587.
      pubmed: 12791997
    73. Kanneganti TD, Lamkanfi M, Núñez G. Intracellular NOD‐like receptors in host defense and disease. Immunity 27, 549‐559.
      pubmed: 17967410
    74. Ogura Y, Inohara N, Benito A, Chen FF, Yamaoka S, Nunez G. Nod2, a Nod1/Apaf‐1 family member that is restricted to monocytes and activates NF‐κB. J. Biol. Chem. 276, 4812‐4818.
      pubmed: 11087742
    75. Chamaillard M, Hashimoto M, Horie Y, Masumoto J, Qiu S, Saab L, Ogura Y, Kawasaki A, Fukase K, Kusumoto S, Valvano MA, Foster SJ, Mak TW, Nuñez G, Inohara N. An essential role for NOD1 in host recognition of bacterial peptidoglycan containing diaminopimelic acid. Nat. Immunol. 4, 702‐707.
      pubmed: 12796777
    76. Clarke TB, Davis KM, Lysenko ES, Zhou AY, Yu Y, Weiser JN. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat. Med. 16, 228‐231.
      pmc: PMC4497535pubmed: 20081863
    77. Racine J, Gerber V, Miskovic Feutz M, Riley CP, Adamec J, Swinburne JE, Couetil LL. Comparison of genomic and proteomic data in recurrent airway obstruction affected horses using ingenuity pathway analysis®. BMC Vet. Res. 7, 48.
      pmc: PMC3174119pubmed: 21843342
    78. Sutterwala FS, Flavell R. NLRC4/IPAF: a CARD carrying member of the NLR family. Clin. Immunol. 130, 2‐6.
      pmc: PMC2630383pubmed: 18819842
    79. Poyet JL, Srinivasula SM, Tnani M, Razmara M, Fernandes‐Alnemri T, Alnemri ES. Identification of Ipaf, a human caspase‐1‐activating protein related to Apaf‐1. J. Biol. Chem. 276, 28309‐28313.
      pubmed: 11390368
    80. Mariathasan S, Newton K, Monack DM, Vucic D, French DM, Lee WP, Roose‐Girma M, Erickson S, Dixit V. Differential activation of the inflammasome by caspase‐1 adaptors ASC and Ipaf. Nature 430, 213‐218.
      pubmed: 15190255
    81. Miao EA, Ernst RK, Dors M, Mao DP, Aderem A. Pseudomonas aeruginosa activates caspase 1 through Ipaf. Proc. Natl. Acad. Sci. U.S.A. 105, 2562‐2567.
      pmc: PMC2268176pubmed: 18256184
    82. Hilbi H, Moss JE, Hersh D, Chen Y, Arondel J, Banerjee S, Flavell R, Yuan J, Sansonetti PJ, Zychlinsky A. Shigella‐induced apoptosis is dependent on caspase‐1 which binds to IpaB. J. Biol. Chem. 273, 32895‐32900.
      pubmed: 9830039
    83. Amer A, Franchi L, Kanneganti TD, Body‐Malapel M, Özören N, Brady G, Meshinchi S, Jagirdar R, Gewirtz A, Akira S, Núñez G. Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf. J. Biol. Chem. 281, 35217‐35223.
      pubmed: 16984919
    84. Miao EA, Alpuche‐Aranda CM, Dors M, Clark AE, Bader MW, Miller SI, Aderem A. Cytoplasmic flagellin activates caspase‐1 and secretion of interleukin 1β via Ipaf. Nat. Immunol. 7, 569‐575.
      pubmed: 16648853
    85. Franchi L, Amer A, Body‐Malapel M, Kanneganti TD, Özören N, Jagirdar R, Inohara N, Vandenabeele P, Bertin J, Coyle A, Grant EP, Núñez G. Cytosolic flagellin requires Ipaf for activation of caspase‐1 and interleukin 1β in salmonella‐infected macrophages. Nat. Immunol. 7, 576‐582.
      pubmed: 16648852
    86. Miao EA, Mao DP, Yudkovsky N, Bonneau R, Lorang CG, Warren SE, Leaf IA, Aderem A. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc. Natl. Acad. Sci. U.S.A. 107, 3076‐3080.
      pmc: PMC2840275pubmed: 20133635
    87. Craven RR, Gao X, Allen IC, Gris D, Bubeck Wardenburg J, McElvania‐Tekippe E, Ting JP, Duncan JA. Staphylococcus aureus α‐hemolysin activates the NLRP3‐inflammasome in human and mouse monocytic cells. PLoS One 4, e7446.
      pmc: PMC2758589pubmed: 19826485
    88. McNeela EA, Burke A, Neill DR, Baxter C, Fernandes VE, Ferreira D, Smeaton S, El‐Rachkidy R, McLoughlin RM, Mori A, Moran B, Fitzgerald KA, Tschopp J, Petrilli V, Andrew PW, Kadioglu A, Lavelle E. Pneumolysin activates the NLRP3 inflammasome and promotes proinflammatory cytokines independently of TLR4. PLoS Pathog. 6, e1001191.
      pmc: PMC2978728pubmed: 21085613
    89. Broz P, Newton K, Lamkanfi M, Mariathasan S, Dixit VM, Monack DM. Redundant roles for inflammasome receptors NLRP3 and NLRC4 in host defense against Salmonella. J. Exp. Med. 207, 1745‐1755.
      pmc: PMC2916133pubmed: 20603313
    90. Bryant C, Fitzgerald KA. Molecular mechanisms involved in inflammasome activation. Trends Cell Biol. 19, 455‐464.
      pubmed: 19716304
    91. Hornung V, Ablasser A, Charrel‐Dennis M, Bauernfeind F, Horvath G, Caffrey DR, Latz E, Fitzgerald K. AIM2 recognizes cytosolic dsDNA and forms a caspase‐1‐activating inflammasome with ASC. Nature 458, 514‐518.
      pmc: PMC2726264pubmed: 19158675
    92. Burckstummer T, Baumann C, Bluml S, Dixit E, Durnberger G, Jahn H, Planyavsky M, Bilban M, Colinge J, Bennett KL, Superti‐Furga G. An orthogonal proteomic‐genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat. Immunol. 10, 266‐272.
      pubmed: 19158679
    93. Choubey D, Walter S, Geng Y, Xin H. Cytoplasmic localization of the interferon‐inducible protein that is encoded by the AIM2 (absent in melanoma) gene from the 200‐gene family. FEBS Lett. 474, 38‐42.
      pubmed: 10828447
    94. Rathinam VAK, Jiang Z, Waggoner SN, Sharma S, Cole LE, Waggoner L, Vanaja SK, Monks BG, Ganesan S, Latz E, Hornung V, Vogel SN, Szomolanyi‐Tsuda E, Fitzgerald K. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11, 395‐402.
      pmc: PMC2887480pubmed: 20351692
    95. Warren SE, Armstrong A, Hamilton MK, Mao DP, Leaf I, Miao E, Aderem A. Cutting edge: cytosolic bacterial DNA activates the inflammasome via Aim2. J. Immunol. 185, 818‐821.
      pmc: PMC2993756pubmed: 20562263
    96. Lien E, Means TK, Heine H, Yoshimura A, Kusumoto S, Fukase K, Fenton MJ, Oikawa M, Qureshi N, Monks B, Finberg RW, Ingalls RR, Golenbock DT. Toll‐like receptor 4 imparts ligand‐specific recognition of bacterial lipopolysaccharide. J. Clin. Invest. 105, 497‐504.
      pmc: PMC289161pubmed: 10683379
    97. Lohmann KL, Vandenplas M, Barton MH, Moore JN. Lipopolysaccharide from Rhodobacter sphaeroides is an agonist in equine cells. J. Endotoxin Res. 9, 33‐37.
      pubmed: 12691616
    98. Bryant CE, Ouellette A, Lohmann K, Vandenplas M, Moore JN, Maskell DJ, Farnfield BA. The cellular Toll‐like receptor 4 antagonist E5531 can act as an agonist in horse whole blood. Vet. Immunol. Immunopathol. 116, 182‐189.
      pubmed: 17320193
    99. Bunnell E, Lynn M, Habet K, Neumann A, Perdomo CA, Friedhoff LT, Rogers SL, Parrillo JE. A lipid A analog, E5531, blocks the endotoxin response in human volunteers with experimental endotoxemia. Crit. Care Med. 28, 2713‐2720.
      pubmed: 10966240
    100. Kawata T, Bristol JR, Rossignol DP, Rose JR, Kobayashi S, Yokohama H, Ishibashi A, Christ WJ, Katayama K, Yamatsu I, Kishi Y. E5531, a synthetic non‐toxic lipid A derivative blocks the immunobiological activities of lipopolysaccharide. Br. J. Pharmacol. 127, 853‐862.
      pmc: PMC1566082pubmed: 10433491
    101. Rossignol DP, Lynn M. Antagonism of in vivo and ex vivo response to endotoxin by E5564, a synthetic lipid A analogue. J. Endotoxin Res. 8, 483‐488.
      pubmed: 12697095
    102. Lynn M, Wong YN, Wheeler JL, Kao RJ, Perdomo CA, Noveck R, Vargas R, D'Angelo T, Gotzkowsky S, McMahon FG, Wasan KM, Rossignol DP. Extended in vivo pharmacodynamic activity of E5564 in normal volunteers with experimental endotoxemia [corrected]. J. Pharmacol. Exp. Ther. 308, 175‐181.
      pubmed: 14566003
    103. Figueiredo MD, Moore JN, Vandenplas ML, Sun W, Murray TF. Effects of the second‐generation synthetic lipid A analogue E5564 on responses to endotoxin in [corrected] equine whole blood and monocytes. Am. J. Vet. Res. 69, 796‐803.
      pubmed: 18518661
    104. Kalil AC, LaRosa SP, Gogate J, Lynn M, Opal SM. Influence of severity of illness on the effects of eritoran tetrasodium (E5564) and on other therapies for severe sepsis. Shock 36, 327‐331.
      pubmed: 21701421
    105. Opal SM. Eritoran trial reaches unfortunate conclusion. ISICEM News pp 8‐9.
    106. Hennessy EJ, Parker AE, O'Neill LA. Targeting Toll‐like receptors: emerging therapeutics?. Nat. Rev. Drug Discov. 9, 293‐307.
      pubmed: 20380038
    107. Spyvee MR, Zhang H, Hawkins LD, Chow JC. Toll‐like receptor 2 antagonists. Part 1: preliminary SAR investigation of novel synthetic phospholipids. Bioorg. Med. Chem. Lett. 15, 5494‐5498.
      pubmed: 16236498
    108. Meng G, Rutz M, Schiemann M, Metzger J, Grabiec A, Schwandner R, Luppa PB, Ebel F, Busch DH, Bauer S, Wagner H, Kirschning CJ. Antagonistic antibody prevents toll‐like receptor 2‐driven lethal shock‐like syndromes. J. Clin. Invest. 113, 1473‐1481.
      pmc: PMC406529pubmed: 15146245
    109. Kirschning CJ, Dreher S, Maass B, Fichte S, Schade J, Koster M, Noack A, Lindenmaier W, Wagner H, Boldicke T. Generation of anti‐TLR2 intrabody mediating inhibition of macrophage surface TLR2 expression and TLR2‐driven cell activation. BMC Biotechnol. 10, 31.
      pmc: PMC2873280pubmed: 20388199
    110. Nic An Ultaigh S, Saber TP, McCormick J, Connolly M, Dellacasagrande J, Keogh B, McCormack W, Reilly M, O'Neill LA, McGuirk P, Fearon U, Veale DJ. Blockade of Toll‐like receptor 2 prevents spontaneous cytokine release from rheumatoid arthritis ex vivo synovial explant cultures. Arthritis Res. Ther. 13, R33.
      pmc: PMC3241377pubmed: 21345222
    111. Arslan F, Smeets MB, O'Neill LA, Keogh B, McGuirk P, Timmers L, Tersteeg C, Hoefer IE, Doevendans PA, Pasterkamp G, de Kleijn DP. Myocardial ischemia/reperfusion injury is mediated by leukocytic toll‐like receptor‐2 and reduced by systemic administration of a novel anti‐toll‐like receptor‐2 antibody. Circulation 121, 80‐90.
      pubmed: 20026776
    112. Takeuchi O, Sato S, Horiuchi T, Hoshino K, Takeda K, Dong Z, Modlin RL, Akira S. Cutting edge: role of Toll‐like receptor 1 in mediating immune response to microbial lipoproteins. J. Immunol. 169, 10‐14.
      pubmed: 12077222
    113. Kwon S, Vandenplas ML, Figueiredo MD, Salter CE, Andrietti AL, Robertson TP, Moore JN, Hurley DJ. Differential induction of Toll‐like receptor gene expression in equine monocytes activated by Toll‐like receptor ligands or TNF‐α. Vet. Immunol. Immunopathol. 138, 213‐217.
      pubmed: 20801527
    114. Alexopoulou L, Thomas V, Schnare M, Lobet Y, Anguita J, Schoen RT, Medzhitov R, Fikrig E, Flavell RA. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1‐ and TLR2‐deficient mice. Nat. Med. 8, 878‐884.
      pubmed: 12091878
    115. Wyllie DH, Kiss‐Toth E, Visintin A, Smith SC, Boussouf S, Segal DM, Duff GW, Dower SK. Evidence for an accessory protein function for Toll‐like receptor 1 in anti‐bacterial responses. J. Immunol. 165, 7125‐7132.
      pubmed: 11120843
    116. Massari P, Henneke P, Ho Y, Latz E, Golenbock DT, Wetzler LM. Cutting edge: immune stimulation by neisserial porins is toll‐like receptor 2 and MyD88 dependent. J. Immunol. 168, 1533‐1537.
      pubmed: 11823477
    117. Aliprantis AO, Yang RB, Mark MR, Suggett S, Devaux B, Radolf JD, Klimpel GR, Godowski P, Zychlinsky A. Cell activation and apoptosis by bacterial lipoproteins through toll‐like receptor‐2. Science 285, 736‐739.
      pubmed: 10426996
    118. Brightbill HD, Libraty DH, Krutzik SR, Yang RB, Belisle JT, Bleharski JR, Maitland M, Norgard MV, Plevy SE, Smale ST, Brennan PJ, Bloom BR, Godowski PJ, Modlin RL. Host defense mechanisms triggered by microbial lipoproteins through toll‐like receptors. Science 285, 732‐736.
      pubmed: 10426995
    119. Opitz B, Schröder NW, Spreitzer I, Michelsen KS, Kirschning CJ, Hallatschek W, Zähringer U, Hartung T, Göbel UB, Schumann RR. Toll‐like receptor‐2 mediates Treponema glycolipid and lipoteichoic acid‐induced NF‐κB translocation. J. Biol. Chem. 276, 22041‐22047.
      pubmed: 11285258
    120. Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ. Peptidoglycan‐ and lipoteichoic acid‐induced cell activation is mediated by toll‐like receptor 2. J. Biol. Chem. 274, 17406‐17409.
      pubmed: 10364168
    121. Underhill DM, Ozinsky A, Smith KD, Aderem A. Toll‐like receptor‐2 mediates mycobacteria‐induced proinflammatory signaling in macrophages. Proc. Natl. Acad. Sci. U.S.A. 96, 14459‐14463.
      pmc: PMC24458pubmed: 10588727
    122. Garton NJ, Gilleron M, Brando T, Dan HH, Giguere S, Puzo G, Prescott JF, Sutcliffe IC. A novel lipoarabinomannan from the equine pathogen Rhodococcus equi. Structure and effect on macrophage cytokine production. J. Biol. Chem. 277, 31722‐31733.
      pubmed: 12072437
    123. Codolo G, Papinutto E, Polenghi A, D'Elios MM, Zanotti G, de Bernard M. Structure and immunomodulatory property relationship in NapA of Borrelia burgdorferi. Biochim. Biophys. Acta 1804, 2191‐2197.
      pubmed: 20851780
    124. Campos MA, Almeida IC, Takeuchi O, Akira S, Valente EP, Procopio DO, Travassos LR, Smith JA, Golenbock DT, Gazzinelli RT. Activation of Toll‐like receptor‐2 by glycosylphosphatidylinositol anchors from a protozoan parasite. J. Immunol. 167, 416‐423.
      pubmed: 11418678
    125. Hajjar AM, O'Mahony DS, Ozinsky A, Underhill DM, Aderem A, Klebanoff SJ, Wilson CB. Cutting edge: functional interactions between toll‐like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol‐soluble modulin. J. Immunol. 166, 15‐19.
      pubmed: 11123271
    126. Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, Schroeder L, Aderem A. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll‐like receptors. Proc. Natl. Acad. Sci. U.S.A. 97, 13766‐13771.
      pmc: PMC17650pubmed: 11095740
    127. Jouault T, Ibata‐Ombetta S, Takeuchi O, Trinel PA, Sacchetti P, Lefebvre P, Akira S, Poulain D. Candida albicans phospholipomannan is sensed through toll‐like receptors. J. Infect. Dis. 188, 165‐172.
      pubmed: 12825186
    128. Werts C, Tapping RI, Mathison JC, Chuang TH, Kravchenko V, Saint Girons I, Haake DA, Godowski PJ, Hayashi F, Ozinsky A, Underhill DM, Kirschning CJ, Wagner H, Aderem A, Tobias PS, Ulevitch RJ. Leptospiral lipopolysaccharide activates cells through a TLR2‐dependent mechanism. Nat. Immunol. 2, 346‐352.
      pubmed: 11276206
    129. Hirschfeld M, Weis JJ, Toshchakov V, Salkowski CA, Cody MJ, Ward DC, Qureshi N, Michalek SM, Vogel SN. Signaling by toll‐like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect. Immun. 69, 1477‐1482.
      pmc: PMC98044pubmed: 11179315
    130. Vabulas RM, Ahmad‐Nejad P, da Costa C, Miethke T, Kirschning CJ, Hacker H, Wagner H. Endocytosed HSP60s use toll‐like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin‐1 receptor signaling pathway in innate immune cells. J. Biol. Chem. 276, 31332‐31339.
      pubmed: 11402040
    131. Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, Stevenson MA, Calderwood SK. Novel signal transduction pathway utilized by extracellular HSP70: role of toll‐like receptor (TLR) 2 and TLR4. J. Biol. Chem. 277, 15028‐15034.
      pubmed: 11836257
    132. Huang QQ, Sobkoviak R, Jockheck‐Clark AR, Shi B, Mandelin AM 2nd, Tak PP, Haines GK 3rd, Nicchitta CV, Pope RM. Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primarily via TLR2 signaling. J. Immunol. 182, 4965‐4973.
      pmc: PMC2814438pubmed: 19342676
    133. Yu M, Wang H, Ding A, Golenbock DT, Latz E, Czura CJ, Fenton MJ, Tracey KJ, Yang H. HMGB1 signals through toll‐like receptor (TLR) 4 and TLR2. Shock 26, 174‐179.
      pubmed: 16878026
    134. Scheibner KA, Lutz MA, Boodoo S, Fenton MJ, Powell JD, Horton MR. Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J. Immunol. 177, 1272‐1281.
      pubmed: 16818787
    135. Gariboldi S, Palazzo M, Zanobbio L, Selleri S, Sommariva M, Sfondrini L, Cavicchini S, Balsari A, Rumio C. Low molecular weight hyaluronic acid increases the self‐defense of skin epithelium by induction of β‐defensin 2 via TLR2 and TLR4. J. Immunol. 181, 2103‐2110.
      pubmed: 18641349
    136. Bieback K, Lien E, Klagge IM, Avota E, Schneider‐Schaulies J, Duprex WP, Wagner H, Kirschning CJ, Ter Meulen V, Schneider‐Schaulies S. Hemagglutinin protein of wild‐type measles virus activates toll‐like receptor 2 signaling. J. Virol. 76, 8729‐8736.
      pmc: PMC136986pubmed: 12163593
    137. Kurt‐Jones EA, Chan M, Zhou S, Wang J, Reed G, Bronson R, Arnold MM, Knipe DM, Finberg RW. Herpes simplex virus 1 interaction with Toll‐like receptor 2 contributes to lethal encephalitis. Proc. Natl. Acad. Sci. U.S.A. 101, 1315‐1320.
      pmc: PMC337050pubmed: 14739339
    138. Compton T, Kurt‐Jones EA, Boehme KW, Belko J, Latz E, Golenbock DT, Finberg RW. Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll‐like receptor 2. J. Virol. 77, 4588‐4596.
      pmc: PMC152130pubmed: 12663765
    139. Murawski MR, Bowen GN, Cerny AM, Anderson LJ, Haynes LM, Tripp RA, Kurt‐Jones EA, Finberg RW. Respiratory syncytial virus activates innate immunity through Toll‐like receptor 2. J. Virol. 83, 1492‐1500.
      pmc: PMC2620898pubmed: 19019963
    140. Zhou S, Kurt‐Jones EA, Mandell L, Cerny A, Chan M, Golenbock DT, Finberg RW. MyD88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection. Eur. J. Immunol. 35, 822‐830.
      pubmed: 15724245
    141. Jeannin P, Bottazzi B, Sironi M, Doni A, Rusnati M, Presta M, Maina V, Magistrelli G, Haeuw JF, Hoeffel G, Thieblemont N, Corvaia N, Garlanda C, Delneste Y, Mantovani A. Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors. Immunity 22, 551‐560.
      pubmed: 15894273
    142. Flo TH, Halaas O, Lien E, Ryan L, Teti G, Golenbock DT, Sundan A, Espevik T. Human Toll‐like receptor 2 mediates monocyte activation by Listeria monocytogenes, but not by group B streptococci or lipopolysaccharide. J. Immunol. 164, 2064‐2069.
      pubmed: 10657659
    143. Dosch SF, Mahajan SD, Collins AR. SARS coronavirus spike protein‐induced innate immune response occurs via activation of the NF‐κB pathway in human monocyte macrophages in vitro. Virus Res. 142, 19‐27.
      pmc: PMC2699111pubmed: 19185596
    144. Tada H, Nemoto E, Shimauchi H, Watanabe T, Mikami T, Matsumoto T, Ohno N, Tamura H, Shibata K, Akashi S, Miyake K, Sugawara S, Takada H. Saccharomyces cerevisiae‐ and Candida albicans‐derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14‐ and Toll‐like receptor 4‐dependent manner. Microbiol. Immunol. 46, 503‐512.
      pubmed: 12222939
    145. Shoham S, Huang C, Chen JM, Golenbock DT, Levitz SM. Toll‐like receptor 4 mediates intracellular signaling without TNF‐α release in response to Cryptococcus neoformans polysaccharide capsule. J. Immunol. 166, 4620‐4626.
      pubmed: 11254720
    146. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T, Miyake K, Freudenberg M, Galanos C, Simon J. Oligosaccharides of Hyaluronan activate dendritic cells via toll‐like receptor 4. J. Exp. Med. 195, 99‐111.
      pmc: PMC2196009pubmed: 11781369
    147. Gaddis DE, Michalek SM, Katz J. Requirement of TLR4 and CD14 in dendritic cell activation by Hemagglutinin B from Porphyromonas gingivalis. Mol. Immunol. 46, 2493‐2504.
      pmc: PMC2763909pubmed: 19540594
    148. Gomi K, Kawasaki K, Kawai Y, Shiozaki M, Nishijima M. Toll‐like receptor 4‐MD‐2 complex mediates the signal transduction induced by flavolipin, an amino acid‐containing lipid unique to Flavobacterium meningosepticum. J. Immunol. 168, 2939‐2943.
      pubmed: 11884465
    149. Morefield GL, Hawkins LD, Ishizaka ST, Kissner TL, Ulrich RG. Synthetic Toll‐like receptor 4 agonist enhances vaccine efficacy in an experimental model of toxic shock syndrome. Clin. Vaccine Immunol. 14, 1499‐1504.
      pmc: PMC2168172pubmed: 17715328
    150. Kawasaki K, Akashi S, Shimazu R, Yoshida T, Miyake K, Nishijima M. Mouse toll‐like receptor 4.MD‐2 complex mediates lipopolysaccharide‐mimetic signal transduction by Taxol. J. Biol. Chem. 275, 2251‐2254.
      pubmed: 10644670
    151. Kurt‐Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, Walsh EE, Freeman MW, Golenbock DT, Anderson LJ, Finberg RW. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat. Immunol. 1, 398‐401.
      pubmed: 11062499
    152. Rassa JC, Meyers JL, Zhang Y, Kudaravalli R, Ross SR. Murine retroviruses activate B cells via interaction with toll‐like receptor 4. Proc. Natl. Acad. Sci. U.S.A. 99, 2281‐2286.
      pmc: PMC122356pubmed: 11854525
    153. Okamura Y, Watari M, Jerud ES, Young DW, Ishizaka ST, Rose J, Chow JC, Strauss JF 3rd. The extra domain A of fibronectin activates Toll‐like receptor 4. J. Biol. Chem. 276, 10229‐10233.
      pubmed: 11150311
    154. Johnson GB, Brunn GJ, Kodaira Y, Platt JL. Receptor‐mediated monitoring of tissue well‐being via detection of soluble heparan sulfate by Toll‐like receptor 4. J. Immunol. 168, 5233‐5239.
      pubmed: 11994480
    155. Smiley ST, King JA, Hancock WW. Fibrinogen stimulates macrophage chemokine secretion through toll‐like receptor 4. J. Immunol. 167, 2887‐2894.
      pubmed: 11509636
    156. Roelofs MF, Boelens WC, Joosten LA, Abdollahi‐Roodsaz S, Geurts J, Wunderink LU, Schreurs BW, van den Berg WB, Radstake TR. Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis. J. Immunol. 176, 7021‐7027.
      pubmed: 16709864
    157. Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW. Toll‐like receptor 4‐dependent activation of dendritic cells by beta‐defensin 2. Science 298, 1025‐1029.
      pubmed: 12411706
    158. Eaves‐Pyles TD, Wong HR, Odoms K, Pyles RB. Salmonella flagellin‐dependent proinflammatory responses are localized to the conserved amino and carboxyl regions of the protein. J. Immunol. 167, 7009‐7016.
      pubmed: 11739521
    159. Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, Takeda K, Akira S. Discrimination of bacterial lipoproteins by Toll‐like receptor 6. Int. Immunol. 13, 933‐940.
      pubmed: 11431423
    160. Henneke P, Takeuchi O, van Strijp JA, Guttormsen HK, Smith JA, Schromm AB, Espevik TA, Akira S, Nizet V, Kasper DL, Golenbock DT. Novel engagement of CD14 and multiple toll‐like receptors by group B streptococci. J. Immunol. 167, 7069‐7076.
      pubmed: 11739528
    161. Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A. Toll‐like receptor 9‐mediated recognition of Herpes simplex virus‐2 by plasmacytoid dendritic cells. J. Exp. Med. 198, 513‐520.
      pmc: PMC2194085pubmed: 12900525
    162. Akira S, Hemmi H. Recognition of pathogen‐associated molecular patterns by TLR family. Immunol. Lett. 85, 85‐95.
      pubmed: 12527213
    163. Leadbetter EA, Rifkin IR, Hohlbaum AM, Beaudette BC, Shlomchik MJ, Marshak‐Rothstein A. Chromatin‐IgG complexes activate B cells by dual engagement of IgM and Toll‐like receptors. Nature 416, 603‐607.
      pubmed: 11948342
    164. Coban C, Ishii KJ, Kawai T, Hemmi H, Sato S, Uematsu S, Yamamoto M, Takeuchi O, Itagaki S, Kumar N, Horii T, Akira S. Toll‐like receptor 9 mediates innate immune activation by the malaria pigment hemozoin. J. Exp. Med. 201, 19‐25.
      pmc: PMC2212757pubmed: 15630134
    165. Girardin SE, Travassos LH, Hervé M, Blanot D, Boneca IG, Philpott DJ, Sansonetti PJ, Mengin‐Lecreulx D. Peptidoglycan molecular requirements allowing detection by Nod1 and Nod2. J. Biol. Chem. 278, 41702‐41708.
      pubmed: 12871942
    166. Tada H, Aiba S, Shibata K, Ohteki T, Takada H. Synergistic effect of Nod1 and Nod2 agonists with toll‐like receptor agonists on human dendritic cells to generate interleukin‐12 and T helper type 1 cells. Infect. Immun. 73, 7967‐7976.
      pmc: PMC1307098pubmed: 16299289
    167. Rajan JV, Rodriguez D, Miao EA, Aderem A. The NLRP3 inflammasome detects encephalomyocarditis virus and vesicular stomatitis virus infection. J. Virol. 85, 4167‐4172.
      pmc: PMC3126243pubmed: 21289120
    168. Allen IC, Scull MA, Moore CB, Holl EK, McElvania‐TeKippe E, Taxman DJ, Guthrie EH, Pickles RJ, Ting JP. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity 30, 556‐565.
      pmc: PMC2803103pubmed: 19362020
    169. Hise AG, Tomalka J, Ganesan S, Patel K, Hall BA, Brown GD, Fitzgerald KA. An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell Host Microbe 5, 487‐497.
      pmc: PMC2824856pubmed: 19454352
    170. Said‐Sadier N, Padilla E, Langsley G, Ojcius DM. Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase. PLoS One 5, e10008.
      pmc: PMC2848854pubmed: 20368800
    171. Kumar H, Kumagai Y, Tsuchida T, Koenig PA, Satoh T, Guo Z, Jang MH, Saitoh T, Akira S, Kawai T. Involvement of the NLRP3 inflammasome in innate and humoral adaptive immune responses to fungal β‐glucan. J. Immunol. 183, 8061‐8067.
      pubmed: 20007575
    172. Martinon F, Agostini L, Meylan E, Tschopp J. Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr. Biol. 14, 1929‐1934.
      pubmed: 15530394
    173. Mariathasan S, Weiss DS, Newton K, McBride J, O'Rourke K, Roose‐Girma M, Lee WP, Weinrauch Y, Monack DM, Dixit VM. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature 440, 228‐232.
      pubmed: 16407890
    174. Walev I, Reske K, Palmer M, Valeva A, Bhakdi S. Potassium‐inhibited processing of IL‐1 beta in human monocytes. EMBO J. 14, 1607‐1614.
      pmc: PMC398253pubmed: 7737113
    175. Gurcel L, Abrami L, Girardin S, Tschopp J, van der Goot FG. Caspase‐1 activation of lipid metabolic pathways in response to bacterial pore‐forming toxins promotes cell survival. Cell 126, 1135‐1145.
      pubmed: 16990137
    176. Dostert C, Guarda G, Romero JF, Menu P, Gross O, Tardivel A, Suva ML, Stehle JC, Kopf M, Stamenkovic I, Corradin G, Tschopp J. Malarial hemozoin is a Nalp3 inflammasome activating danger signal. PLoS One 4, e6510.
      pmc: PMC2714977pubmed: 19652710
    177. Warren SE, Mao DP, Rodriguez AE, Miao EA, Aderem A. Multiple Nod‐like receptors activate caspase 1 during Listeria monocytogenes infection. J. Immunol. 180, 7558‐7564.
      pmc: PMC2991040pubmed: 18490757
    178. Kanneganti TD, Body‐Malapel M, Amer A, Park JH, Whitfield J, Franchi L, Taraporewala ZF, Miller D, Patton JT, Inohara N, Núñez G. Critical role for Cryopyrin/Nalp3 in activation of caspase‐1 in response to viral infection and double‐stranded RNA. J. Biol. Chem. 281, 36560‐36568.
      pubmed: 17008311
    179. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout‐associated uric acid crystals activate the NALP3 inflammasome. Nature 440, 237‐241.
      pubmed: 16407889
    180. Dostert C, Petrilli V, Van Bruggen R, Steele C, Mossman BT, Tschopp J. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science 320, 674‐677.
      pmc: PMC2396588pubmed: 18403674
    181. Kool M, Petrilli V, De Smedt T, Rolaz A, Hammad H, van Nimwegen M, Bergen IM, Castillo R, Lambrecht BN, Tschopp J. Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome. J. Immunol. 181, 3755‐3759.
      pubmed: 18768827
    182. Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ, Golenbock DT. The NALP3 inflammasome is involved in the innate immune response to amyloid‐β. Nat. Immunol. 9, 857‐865.
      pmc: PMC3101478pubmed: 18604209
    183. Tomalka J, Ganesan S, Azodi E, Patel K, Majmudar P, Hall BA, Fitzgerald KA, Hise AG. A novel role for the NLRC4 inflammasome in mucosal defenses against the fungal pathogen Candida albicans. PLoS Pathog. 7, e1002379.
      pmc: PMC3234225pubmed: 22174673
    184. Suzuki T, Franchi L, Toma C, Ashida H, Ogawa M, Yoshikawa Y, Mimuro H, Inohara N, Sasakawa C, Nunez G. Differential regulation of caspase‐1 activation, pyroptosis, and autophagy via Ipaf and ASC in Shigella‐infected macrophages. PLoS Pathog. 3, e111.
      pmc: PMC1941748pubmed: 17696608

    Citations

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      doi: 10.3390/ani14243660pubmed: 39765564google scholar: lookup
    2. Gong Z, Mao W, Zhao J, Ren P, Yu Z, Bai Y, Wang C, Liu Y, Feng S, Hasi S. TLR2 and NLRP3 Orchestrate Regulatory Roles in Escherichia coli Infection-Induced Septicemia in Mouse Models. J Innate Immun 2024;16(1):513-528.
      doi: 10.1159/000541819pubmed: 39406206google scholar: lookup
    3. Hasankhani A, Bahrami A, Sheybani N, Fatehi F, Abadeh R, Ghaem Maghami Farahani H, Bahreini Behzadi MR, Javanmard G, Isapour S, Khadem H, Barkema HW. Integrated Network Analysis to Identify Key Modules and Potential Hub Genes Involved in Bovine Respiratory Disease: A Systems Biology Approach. Front Genet 2021;12:753839.
      doi: 10.3389/fgene.2021.753839pubmed: 34733317google scholar: lookup
    4. Mendoza Garcia FJ, Gonzalez-De Cara C, Aguilera-Aguilera R, Buzon-Cuevas A, Perez-Ecija A. Meloxicam ameliorates the systemic inflammatory response syndrome associated with experimentally induced endotoxemia in adult donkeys. J Vet Intern Med 2020 Jul;34(4):1631-1641.
      doi: 10.1111/jvim.15783pubmed: 32463537google scholar: lookup
    5. Taylor S. A review of equine sepsis. Equine Vet Educ 2015 Feb;27(2):99-109.
      doi: 10.1111/eve.12290pubmed: 32313390google scholar: lookup
    6. Sheats MK. A Comparative Review of Equine SIRS, Sepsis, and Neutrophils. Front Vet Sci 2019;6:69.
      doi: 10.3389/fvets.2019.00069pubmed: 30931316google scholar: lookup
    7. Cao D, Pi J, Shan Y, Tang Y, Zhou P. Anti-inflammatory effect of Resolvin D1 on LPS-treated MG-63 cells. Exp Ther Med 2018 Nov;16(5):4283-4288.
      doi: 10.3892/etm.2018.6721pubmed: 30402165google scholar: lookup
    8. Parkinson NJ, Buechner-Maxwell VA, Witonsky SG, Pleasant RS, Werre SR, Ahmed SA. Characterization of basal and lipopolysaccharide-induced microRNA expression in equine peripheral blood mononuclear cells using Next-Generation Sequencing. PLoS One 2017;12(5):e0177664.
      doi: 10.1371/journal.pone.0177664pubmed: 28552958google scholar: lookup
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