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Home / Equine Research Bank / Sci Rep / Host-directed therapy in foals can enhance functional innate...
Scientific reports2021; 11(1); 2483; doi: 10.1038/s41598-021-82049-y

Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia.

Abstract: Pneumonia caused by the intracellular bacterium Rhodococcus equi is an important cause of disease and death in immunocompromised hosts, especially foals. Antibiotics are the standard of care for treating R. equi pneumonia in foals, and adjunctive therapies are needed. We tested whether nebulization with TLR agonists (PUL-042) in foals would improve innate immunity and reduce the severity and duration of pneumonia following R. equi infection. Neonatal foals (n = 48) were nebulized with either PUL-042 or vehicle, and their lung cells infected ex vivo. PUL-042 increased inflammatory cytokines in BAL fluid and alveolar macrophages after ex vivo infection with R. equi. Then, the in vivo effects of PUL-042 on clinical signs of pneumonia were examined in 22 additional foals after intrabronchial challenge with R. equi. Foals infected and nebulized with PUL-042 or vehicle alone had a shorter duration of clinical signs of pneumonia and smaller pulmonary lesions when compared to non-nebulized foals. Our results demonstrate that host-directed therapy can enhance neonatal immune responses against respiratory pathogens and reduce the duration and severity of R. equi pneumonia.
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Publication Date: 2021-01-28 PubMed ID: 33510265PubMed Central: PMC7844249DOI: 10.1038/s41598-021-82049-yGoogle Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 study explores using host-directed therapy, specifically nebulization with TLR agonists (PUL-042), to improve the immunity of foals against pneumonia caused by Rhodococcus equi and reduce the severity of the disease. Trials showed that PUL-042 increased inflammatory cytokines, and foals treated with such had less severe and shorter-lived symptoms of pneumonia.

Study Overview

  • This research primarily aims to find effective remedies for pneumonia in foals, especially pneumonia caused by the intracellular bacterium Rhodococcus equi, which is notably harmful for those with compromised immune systems.
  • Typically, antibiotics are used to cure R. equi pneumonia but additional treatments are needed. This study tests whether PUL-042, a Toll-Like Receptor (TLR) agonist, delivered through nebulization can not only boost the foals’ innate immunity but lessen the severity and duration of the pneumonia following an R. equi infection.

Methodology and Findings

  • The study involved a total of 70 foals.
  • 48 neonatal foals were treated with a nebulizer filled with either PUL-042 or a control solution, and then their lung cells were infected in a laboratory setting.
  • The results showed that PUL-042 increased the presence of inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid and the alveolar macrophages after ex vivo infection with R. equi. This signifies a higher immune response in the organisms.
  • To further verify the results, an in vivo trial was conducted on 22 more foals. They were intrabronchially challenged with R. equi, after which their pneumonia signs were observed.
  • Those infected and treated with PUL-042 or just the control solution had less severe symptoms of pneumonia and their pulmonary lesions were smaller in comparison to the foals who were not nebulized.

Conclusions

  • This study demonstrated that host-directed therapy can ameliorate neonatal immune responses against respiratory pathogens, resulting in less severe and shorter durations of R. equi pneumonia.
  • As a recommendation for practice, it suggests that nebulization with TLR agonist PUL-042 can potentially serve as an adjunctive therapy alongside antibiotics for foals afflicted by R. equi pneumonia.

Cite This Article

APA
Bordin AI, Cohen ND, Giguère S, Bray JM, Berghaus LJ, Scott B, Johnson R, Hook M. (2021). Host-directed therapy in foals can enhance functional innate immunity and reduce severity of Rhodococcus equi pneumonia. Sci Rep, 11(1), 2483. https://doi.org/10.1038/s41598-021-82049-y

Publication

Scientific reports
ISSN: 2045-2322
NlmUniqueID: 101563288
Country: England
Language: English
Volume: 11
Issue: 1
Pages: 2483

Researcher Affiliations

Bordin, Angela I
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA. abordin@cvm.tamu.edu.
Cohen, Noah D
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Giguère, Steve
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Bray, Jocelyne M
  • Equine Infectious Disease Laboratory, Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX, USA.
Berghaus, Londa J
  • Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
Scott, Brenton
  • Pulmotect, Inc., Houston, TX, USA.
Johnson, Rena
  • Pulmotect, Inc., Houston, TX, USA.
Hook, Magnus
  • Institute of Biosciences and Technology, Center for Infectious and Inflammatory Diseases, Texas A&M University, Houston, TX, USA.

MeSH Terms

  • Actinomycetales Infections / drug therapy
  • Actinomycetales Infections / immunology
  • Actinomycetales Infections / pathology
  • Actinomycetales Infections / veterinary
  • Animals
  • Horse Diseases / drug therapy
  • Horse Diseases / immunology
  • Horse Diseases / pathology
  • Horses / immunology
  • Horses / microbiology
  • Immunity, Innate / drug effects
  • Lipopeptides / pharmacology
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / pathology
  • Oligodeoxyribonucleotides / pharmacology
  • Pneumonia, Bacterial / drug therapy
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Bacterial / pathology
  • Pneumonia, Bacterial / veterinary
  • Rhodococcus equi / immunology
  • Severity of Illness Index
  • Toll-Like Receptor 2 / agonists
  • Toll-Like Receptor 6 / agonists
  • Toll-Like Receptor 9 / agonists

Conflict of Interest Statement

Dr. Hook has received compensation as a member of the scientific advisory board of Pulmotect, Inc. and owns stock options in the company. Drs. Scott and Johnson are employees of Pulmotect, Inc. and own stock options in the company. The other authors declare no competing interests.

References

This article includes 66 references
  1. Takai S. Correlation of in vitro properties of Rhodococcus (Corynebacterium) equi with virulence for mice. Microbiol. Immunol. 1985;29(12):1175–1184.
    doi: 10.1111/j.1348-0421.1985.tb00907.xpubmed: 3831718google scholar: lookup
  2. Horowitz ML. Application of Sartwell's model (lognormal distribution of incubation periods) to age at onset and age at death of foals with Rhodococcus equi pneumonia as evidence of perinatal infection. J. Vet. Intern. Med. 2001;15(3):171–175.
    pubmed: 11380023
  3. Sanz M. The effect of bacterial dose and foal age at challenge on Rhodococcus equi infection. Vet. Microbiol. 2013;167(3–4):623–631.
    doi: 10.1016/j.vetmic.2013.09.018pubmed: 24139178google scholar: lookup
  4. Liu T. Basal and stimulus-induced cytokine expression is selectively impaired in peripheral blood mononuclear cells of newborn foals. Vaccine 2009;27(5):674–683.
    doi: 10.1016/j.vaccine.2008.11.040pubmed: 19056444google scholar: lookup
  5. Flaminio MJ. Characterization of peripheral blood and pulmonary leukocyte function in healthy foals. Vet. Immunol. Immunopathol. 2000;73(3–4):267–285.
    doi: 10.1016/S0165-2427(00)00149-5pubmed: 10713340google scholar: lookup
  6. Flaminio MJ. The effect of CpG-ODN on antigen presenting cells of the foal. J. Immune Based Ther. Vaccines 2007;5:1.
    doi: 10.1186/1476-8518-5-1pmc: PMC1797044pubmed: 17254326google scholar: lookup
  7. Boyd NK. Temporal changes in cytokine expression of foals during the first month of life. Vet. Immunol. Immunopathol. 2003;92(1–2):75–85.
    doi: 10.1016/S0165-2427(03)00021-7pubmed: 12628765google scholar: lookup
  8. Breathnach CC. Foals are interferon gamma-deficient at birth. Vet. Immunol. Immunopathol. 2006;112(3–4):199–209.
    doi: 10.1016/j.vetimm.2006.02.010pubmed: 16621024google scholar: lookup
  9. Flaminio MJ. Foal monocyte-derived dendritic cells become activated upon Rhodococcus equi infection. Clin. Vaccine Immunol. 2009;16(2):176–183.
    doi: 10.1128/CVI.00336-08pmc: PMC2643540pubmed: 19109450google scholar: lookup
  10. Levy O. Innate immunity of the newborn: Basic mechanisms and clinical correlates. Nat. Rev. Immunol. 2007;7(5):379–390.
    doi: 10.1038/nri2075pubmed: 17457344google scholar: lookup
  11. Cywes-Bentley C. Antibody to poly-N-acetyl glucosamine provides protection against intracellular pathogens: Mechanism of action and validation in horse foals challenged with Rhodococcus equi. PLoS Pathog. 2018;14(7):e1007160.
    doi: 10.1371/journal.ppat.1007160pmc: PMC6053243pubmed: 30024986google scholar: lookup
  12. Giguere S. Evaluation of a commercially available hyperimmune plasma product for prevention of naturally acquired pneumonia caused by Rhodococcus equi in foals. J. Am. Vet. Med. Assoc. 2002;220(1):59–63.
    doi: 10.2460/javma.2002.220.59pubmed: 12680449google scholar: lookup
  13. Caston SS. Effect of hyperimmune plasma on the severity of pneumonia caused by Rhodococcus equi in experimentally infected foals. Vet. Ther. 2006;7(4):361–375.
    pubmed: 17216591
  14. Hurley JR, Begg AP. Failure of hyperimmune plasma to prevent pneumonia caused by Rhodococcus equi in foals. Aust. Vet. J. 1995;72(11):418–420.
    doi: 10.1111/j.1751-0813.1995.tb06192.xpubmed: 8929188google scholar: lookup
  15. Sanz MG. Administration of commercial Rhodococcus equi specific hyperimmune plasma results in variable amounts of IgG against pathogenic bacteria in foals. Vet. Rec. 2014;175(19):485.
    doi: 10.1136/vr.102594pubmed: 25117301google scholar: lookup
  16. Giguere S. Diagnosis, treatment, control, and prevention of infections caused by Rhodococcus equi in foals. J. Vet. Intern. Med. 2011;25(6):1209–1220.
    doi: 10.1111/j.1939-1676.2011.00835.xpubmed: 22092608google scholar: lookup
  17. Cohen ND, Giguère S. Rhodococcus equi foal pneumonia. 2009. pp. 235–246.
  18. Burton AJ. Macrolide- and rifampin-resistant Rhodococcus equi on a horse breeding farm, Kentucky, USA. Emerg. Infect. Dis. 2013;19(2):282–285.
    doi: 10.3201/eid1902.121210pmc: PMC3559061pubmed: 23347878google scholar: lookup
  19. Huber L. Prevalence and risk factors associated with emergence of Rhodococcus equi resistance to macrolides and rifampicin in horse-breeding farms in Kentucky, USA. Vet. Microbiol. 2019;235:243–247.
    doi: 10.1016/j.vetmic.2019.07.010pubmed: 31383308google scholar: lookup
  20. Huber L. Emergence of resistance to macrolides and rifampin in clinical isolates of Rhodococcus equi from foals in central Kentucky, 1995 to 2017. Antimicrob. Agents Chemother. 2019.
    doi: 10.1128/AAC.01714-18pmc: PMC6325176pubmed: 30373803google scholar: lookup
  21. Huber L. Identification of macrolide- and rifampicin-resistant Rhodococcus equi in environmental samples from equine breeding farms in central Kentucky during 2018. Vet. Microbiol. 2019;232:74–78.
    doi: 10.1016/j.vetmic.2019.04.008pubmed: 31030848google scholar: lookup
  22. Alvarez-Narvaez S. A common practice of widespread antimicrobial use in horse production promotes multi-drug resistance. Sci. Rep. 2020;10(1):911.
    doi: 10.1038/s41598-020-57479-9pmc: PMC6976650pubmed: 31969575google scholar: lookup
  23. Giguere S. Determination of the prevalence of antimicrobial resistance to macrolide antimicrobials or rifampin in Rhodococcus equi isolates and treatment outcome in foals infected with antimicrobial-resistant isolates of R. equi. J. Am. Vet. Med. Assoc. 2010;237(1):74–81.
    doi: 10.2460/javma.237.1.74pubmed: 20590498google scholar: lookup
  24. Jacks SS, Giguere S, Nguyen A. In vitro susceptibilities of Rhodococcus equi and other common equine pathogens to azithromycin, clarithromycin, and 20 other antimicrobials. Antimicrob. Agents Chemother. 2003;47(5):1742–1745.
    doi: 10.1128/AAC.47.5.1742-1745.2003pmc: PMC153307pubmed: 12709351google scholar: lookup
  25. Womble A. Pulmonary disposition of tilmicosin in foals and in vitro activity against Rhodococcus equi and other common equine bacterial pathogens. J. Vet. Pharmacol. Ther. 2006;29(6):561–568.
    doi: 10.1111/j.1365-2885.2006.00804.xpubmed: 17083461google scholar: lookup
  26. Chaffin MK, Cohen ND, Martens RJ. Chemoprophylactic effects of azithromycin against Rhodococcus equi-induced pneumonia among foals at equine breeding farms with endemic infections. J. Am. Vet. Med. Assoc. 2008;232(7):1035–1047.
    doi: 10.2460/javma.232.7.1035pubmed: 18380623google scholar: lookup
  27. Ingrid W. Experimental model of equine alveolar macrophage stimulation with TLR ligands. Vet. Immunol. Immunopathol. 2013;155(1–2):3037.
    pubmed: 23815824
  28. Mak T, Saunders ME. Innate immunity. 2006. pp. 69–92.
  29. Bordin AI. Neutrophil function of neonatal foals is enhanced in vitro by CpG oligodeoxynucleotide stimulation. Vet. Immunol. Immunopathol. 2012;145(1–2):290–297.
    doi: 10.1016/j.vetimm.2011.11.012pubmed: 22197007google scholar: lookup
  30. Cohen ND. Intramuscular administration of a synthetic CpG-oligodeoxynucleotide modulates functional 1 responses of neutrophils of neonatal foals. PLoS ONE 2014;9:e109865.
    doi: 10.1371/journal.pone.0109865pmc: PMC4198146pubmed: 25333660google scholar: lookup
  31. Liu M. Activation of foal neutrophils at different ages by CpG oligodeoxynucleotides and Rhodococcus equi. Cytokine 2009;48(3):280–289.
    doi: 10.1016/j.cyto.2009.08.012pubmed: 19819162google scholar: lookup
  32. Darrah PA. Cooperation between reactive oxygen and nitrogen intermediates in killing of Rhodococcus equi by activated macrophages. Infect. Immunol. 2000;68(6):3587–3593.
    doi: 10.1128/IAI.68.6.3587-3593.2000pmc: PMC97647pubmed: 10816516google scholar: lookup
  33. Chan J. Killing of virulent Mycobacterium tuberculosis by reactive nitrogen intermediates produced by activated murine macrophages. J. Exp. Med. 1992;175(4):1111–1122.
    doi: 10.1084/jem.175.4.1111pmc: PMC2119182pubmed: 1552282google scholar: lookup
  34. Herbst S, Schaible UE, Schneider BE. Interferon gamma activated macrophages kill mycobacteria by nitric oxide induced apoptosis. PLoS ONE 2011;6(5):e19105.
    doi: 10.1371/journal.pone.0019105pmc: PMC3085516pubmed: 21559306google scholar: lookup
  35. Darrah PA. Innate immune responses to Rhodococcus equi. J. Immunol. 2004;173(3):1914–1924.
    doi: 10.4049/jimmunol.173.3.1914pubmed: 15265925google scholar: lookup
  36. Drennan MB. Toll-like receptor 2-deficient mice succumb to Mycobacterium tuberculosis infection. Am. J. Pathol. 2004;164(1):49–57.
    doi: 10.1016/S0002-9440(10)63095-7pmc: PMC1602241pubmed: 14695318google scholar: lookup
  37. Leiva-Juarez MM. Combined aerosolized Toll-like receptor ligands are an effective therapeutic agent against influenza pneumonia when co-administered with oseltamivir. Eur. J. Pharmacol. 2018;818:191–197.
    doi: 10.1016/j.ejphar.2017.10.035pmc: PMC5742311pubmed: 29066417google scholar: lookup
  38. Kirkpatrick CT. Inducible lung epithelial resistance requires multisource reactive oxygen species generation to protect against viral infections. MBio 2018;9(3):e00696.
    doi: 10.1128/mBio.00696-18pmc: PMC5954225pubmed: 29764948google scholar: lookup
  39. Leiva-Juarez MM. Inducible epithelial resistance protects mice against leukemia-associated pneumonia. Blood 2016;128(7):982–992.
    doi: 10.1182/blood-2016-03-708511pmc: PMC4990857pubmed: 27317793google scholar: lookup
  40. Cleaver JO. Lung epithelial cells are essential effectors of inducible resistance to pneumonia. Mucosal. Immunol. 2014;7(1):78–88.
    doi: 10.1038/mi.2013.26pmc: PMC3735803pubmed: 23632328google scholar: lookup
  41. Tuvim MJ. Synergistic TLR2/6 and TLR9 activation protects mice against lethal influenza pneumonia. PLoS ONE 2012;7(1):e30596.
    doi: 10.1371/journal.pone.0030596pmc: PMC3267724pubmed: 22299046google scholar: lookup
  42. Duggan JM. Synergistic interactions of TLR2/6 and TLR9 induce a high level of resistance to lung infection in mice. J. Immunol. 2011;186(10):5916–5926.
    doi: 10.4049/jimmunol.1002122pmc: PMC3654378pubmed: 21482737google scholar: lookup
  43. Roca FJ, Ramakrishnan L. TNF dually mediates resistance and susceptibility to mycobacteria via mitochondrial reactive oxygen species. Cell 2013;153(3):521–534.
    doi: 10.1016/j.cell.2013.03.022pmc: PMC3790588pubmed: 23582643google scholar: lookup
  44. Werley MS. Toxicological assessment of a prototype e-cigaret device and three flavor formulations: A 90-day inhalation study in rats. Inhal. Toxicol. 2016;28(1):22–38.
    doi: 10.3109/08958378.2015.1130758pmc: PMC4778541pubmed: 26787428google scholar: lookup
  45. Hwang JH. Electronic cigarette inhalation alters innate immunity and airway cytokines while increasing the virulence of colonizing bacteria. J. Mol. Med. (Berl.) 2016;94(6):667–679.
    doi: 10.1007/s00109-016-1378-3pubmed: 26804311google scholar: lookup
  46. Garcia-Arcos I. Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner. Thorax 2016;71(12):1119–1129.
    doi: 10.1136/thoraxjnl-2015-208039pmc: PMC5136722pubmed: 27558745google scholar: lookup
  47. Clapp PW. Flavored e-cigarette liquids and cinnamaldehyde impair respiratory innate immune cell function. Am. J. Physiol. Lung Cell Mol. Physiol. 2017;313(2):L278–L292.
    doi: 10.1152/ajplung.00452.2016pmc: PMC5582929pubmed: 28495856google scholar: lookup
  48. Higham A. Electronic cigarette exposure triggers neutrophil inflammatory responses. Respir. Res. 2016;17(1):56.
    doi: 10.1186/s12931-016-0368-xpmc: PMC4869345pubmed: 27184092google scholar: lookup
  49. Scott A. Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages. Thorax 2018;73(12):1161–1169.
    doi: 10.1136/thoraxjnl-2018-211663pmc: PMC6269646pubmed: 30104262google scholar: lookup
  50. Reidel B. E-Cigarette use causes a unique innate immune response in the lung, involving increased neutrophilic activation and altered mucin secretion. Am. J. Respir. Crit. Care Med. 2018;197(4):492–501.
    doi: 10.1164/rccm.201708-1590OCpmc: PMC5821909pubmed: 29053025google scholar: lookup
  51. Ween MP. Phagocytosis and inflammation: Exploring the effects of the components of E-cigarette vapor on macrophages. Physiol. Rep. 2017;5(16):e13370.
    doi: 10.14814/phy2.13370pmc: PMC5582261pubmed: 28867672google scholar: lookup
  52. Escobar YH. In vitro toxicity and chemical characterization of aerosol derived from electronic cigarette humectants using a newly developed exposure system. Chem. Res. Toxicol. 2020;33(7):1677–1688.
    doi: 10.1021/acs.chemrestox.9b00490pmc: PMC11391858pubmed: 32223225google scholar: lookup
  53. Reuschl AK. Innate activation of human primary epithelial cells broadens the host response to Mycobacterium tuberculosis in the airways. PLoS Pathog. 2017;13(9):e1006577.
    doi: 10.1371/journal.ppat.1006577pmc: PMC5605092pubmed: 28863187google scholar: lookup
  54. Remuzgo-Martinez S. Induction of proinflammatory cytokines in human lung epithelial cells during Rhodococcus equi infection. J. Med. Microbiol. 2013;62(Pt 8):1144–1152.
    doi: 10.1099/jmm.0.056234-0pubmed: 23699060google scholar: lookup
  55. Ramos-Vivas J. Rhodococcus equi human clinical isolates enter and survive within human alveolar epithelial cells. Microbes Infect. 2011;13(5):438–446.
    doi: 10.1016/j.micinf.2011.01.003pubmed: 21262372google scholar: lookup
  56. Folmar CN. In vitro evaluation of complement deposition and opsonophagocytic killing of Rhodococcus equi mediated by poly-N-acetyl glucosamine hyperimmune plasma compared to commercial plasma products. J. Vet. Intern. Med. 2019;33(3):1493–1499.
    doi: 10.1111/jvim.15511pmc: PMC6524092pubmed: 31034109google scholar: lookup
  57. Rocha JN. PNAG-specific equine IgG1 mediates significantly greater opsonization and killing of Prescottella equi (formerly Rhodococcus equi) than does IgG4/7. Vaccine 2019;37(9):1142–1150.
    doi: 10.1016/j.vaccine.2019.01.028pmc: PMC8314964pubmed: 30691984google scholar: lookup
  58. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 1999;340(6):448–454.
    doi: 10.1056/NEJM199902113400607pubmed: 9971870google scholar: lookup
  59. Hostetter SJ. Age-related variation in the cellular composition of equine bronchoalveolar lavage fluid. Vet. Clin. Pathol. 2017;46(2):344–353.
    doi: 10.1111/vcp.12473pmc: PMC10629498pubmed: 28346682google scholar: lookup
  60. Clement CG. Stimulation of lung innate immunity protects against lethal pneumococcal pneumonia in mice. Am. J. Respir. Crit. Care Med. 2008;177(12):1322–1330.
    doi: 10.1164/rccm.200607-1038OCpmc: PMC2427056pubmed: 18388354google scholar: lookup
  61. Berghaus LJ, Giguere S, Sturgill TL. Effects of age and macrophage lineage on intracellular survival and cytokine induction after infection with Rhodococcus equi. Vet. Immunol. Immunopathol. 2014;160(1–2):41–50.
    doi: 10.1016/j.vetimm.2014.03.010pubmed: 24736188google scholar: lookup
  62. Rocha JN. Oral administration of electron-beam inactivated Rhodococcus equi failed to protect foals against intrabronchial infection with live, virulent R. equi. PLoS ONE 2016;11(2):e0148111.
    doi: 10.1371/journal.pone.0148111pmc: PMC4735123pubmed: 26828865google scholar: lookup
  63. Halbert ND. Evaluation of a multiplex polymerase chain reaction assay for simultaneous detection of Rhodococcus equi and the vapA gene. Am. J. Vet. Res. 2005;66(8):1380–1385.
    doi: 10.2460/ajvr.2005.66.1380pubmed: 16173481google scholar: lookup
  64. Alfaro VY. Safety, tolerability, and biomarkers of the treatment of mice with aerosolized Toll-like receptor ligands. Front. Pharmacol. 2014;5:8.
    doi: 10.3389/fphar.2014.00008pmc: PMC3915096pubmed: 24567720google scholar: lookup
  65. Evans SE. Inhaled innate immune ligands to prevent pneumonia. Br. J. Pharmacol. 2011;163(1):195–206.
    doi: 10.1111/j.1476-5381.2011.01237.xpmc: PMC3085878pubmed: 21250981google scholar: lookup
  66. Berghaus LJ. Effects of priming with cytokines on intracellular survival and replication of Rhodococcus equi in equine macrophages. Cytokine 2018;102:7–11.
    doi: 10.1016/j.cyto.2017.12.011pubmed: 29245049google scholar: lookup
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