FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Clin Diagn Lab Immunol / Cytokine gene expression by peripheral blood leukocytes in h...
Clinical and diagnostic laboratory immunology2002; 9(5); 1079-1084; doi: 10.1128/cdli.9.5.1079-1084.2002

Cytokine gene expression by peripheral blood leukocytes in horses experimentally infected with Anaplasma phagocytophila.

Abstract: Human granulocytic ehrlichiosis (HGE), a tick-borne zoonosis, is caused by an obligatory intragranulocytic bacterium, the HGE agent, a strain of Anaplasma phagocytophila. The equine model of HGE is considered valuable in understanding pathogenic and immune mechanisms of HGE. In the present study, cytokine mRNA expression by peripheral blood leukocytes (PBLs) in horses was examined during the course of infection by intravenous inoculation of A. phagocytophila or by allowing feeding by infected ticks. The p44 genes encoding the major outer membrane protein P44s of A. phagocytophila were detected by PCR in PBLs of all four horses from 4 to 20 days postexposure. During the 20-day infection period, interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) mRNA expression was upregulated in PBLs of all four horses, and IL-8 mRNA expression was upregulated in three horses. Gamma interferon, IL-10, and IL-12 p35 mRNAs were weakly expressed in only one horse each. IL-2, IL-4, IL-6, and IL-12 p40 mRNA expression, however, could not be detected in the PBLs of any of the four horses. These results suggest that IL-1beta, TNF-alpha, and IL-8 generation during A. phagocytophila infection has a primary role in HGE pathogenesis and immunomodulation.
Get Full Text
Publication Date: 2002-09-03 PubMed ID: 12204963PubMed Central: PMC120081DOI: 10.1128/cdli.9.5.1079-1084.2002Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • U.S. Gov't
  • P.H.S.

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.

This research discusses the examination of cytokine mRNA expression by peripheral blood leukocytes in horses during an infection by Anaplasma phagocytophila. It highlights the role of IL-1beta, TNF-alpha, and IL-8 generation during infection and their impact on the disease’s pathogenesis and immunomodulation.

Research Details

  • The paper presents a study on the equine model of Human granulocytic ehrlichiosis (HGE), a disease caused by a strain of Anaplasma phagocytophila, transferred through tick bites.
  • The research primarily focuses on studying cytokine mRNA expression by peripheral blood leukocytes during the course of infection. The goal is to better understand the disease’s pathogenic and immune mechanisms.

Testing Approach

  • Four horses were infected with A. phagocytophila either through intravenous inoculation or by allowing feeding by infected ticks.
  • The p44 genes, responsible for encoding the major outer membrane protein P44s of A. phagocytophila, were detected through PCR in the leukocytes of all four horses. This confirms successful infection.

Results and Observations

  • During the 20-day infection period, increased mRNA expression of IL-1beta, TNF-alpha, and IL-8 was observed in the horses’ leukocytes. This suggests that these cytokines are primarily involved in the immune response against A. phagocytophila.
  • Contrarily, other cytokines such as Gamma interferon, IL-10, and IL-12 p35 were weakly expressed in only one horse each, suggesting a weaker involvement in the immune response.
  • IL-2, IL-4, IL-6, and IL-12 p40 mRNA expression couldn’t be detected in any of the horses, indicating their minimal contribution during the infection.

Implications

  • The findings indicate that IL-1beta, TNF-alpha, and IL-8 play a crucial role in the pathogenesis of HGE and the immune modulations during the disease.
  • Understanding the role of cytokines in the immune response against A. phagocytophila might help design better treatment strategies for HGE in the future.

Cite This Article

APA
Kim HY, Mott J, Zhi N, Tajima T, Rikihisa Y. (2002). Cytokine gene expression by peripheral blood leukocytes in horses experimentally infected with Anaplasma phagocytophila. Clin Diagn Lab Immunol, 9(5), 1079-1084. https://doi.org/10.1128/cdli.9.5.1079-1084.2002

Publication

Clinical and diagnostic laboratory immunology
ISSN: 1071-412X
NlmUniqueID: 9421292
Country: United States
Language: English
Volume: 9
Issue: 5
Pages: 1079-1084

Researcher Affiliations

Kim, Hyung-Yong
  • Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210-1093, USA.
Mott, Jason
    Zhi, Ning
      Tajima, Tomoko
        Rikihisa, Yasuko

          MeSH Terms

          • Anaplasma phagocytophilum / immunology
          • Animals
          • Bacterial Outer Membrane Proteins / genetics
          • Cytokines / genetics
          • Disease Models, Animal
          • Ehrlichiosis / immunology
          • Female
          • Fluorescent Antibody Technique, Indirect
          • Gene Expression / immunology
          • Horses
          • Leukocytes / microbiology
          • Leukocytes / physiology
          • Male
          • RNA, Messenger / analysis
          • Tick-Borne Diseases / immunology

          Grant Funding

          • R01 AI030010 / NIAID NIH HHS
          • R56 AI030010 / NIAID NIH HHS
          • AI30010 / NIAID NIH HHS
          • AI40934 / NIAID NIH HHS

          References

          This article includes 37 references
          1. Akkoyunlu M, Fikrig E. Gamma interferon dominates the murine cytokine response to the agent of human granulocytic ehrlichiosis and helps to control the degree of early rickettsemia.. Infect. Immun. 2000;68:1827-1833.
            pmc: PMC97354pubmed: 10722570
          2. Akkoyunlu M, Malawista SE, Anguita J, Fikrig E. Exploitation of interleukin-8-induced neutrophil chemotaxis by the agent of human granulocytic ehrlichiosis.. Infect. Immun. 2001;69:5577-5588.
            pmc: PMC98672pubmed: 11500432
          3. Bakken JS, Krueth J, Wilson-Nordskog C, Tilden RL, Asanovich K, Dumler JS. Clinical and laboratory characteristics of human granulocytic ehrlichiosis.. JAMA 1996;275:199-205.
            pubmed: 8604172
          4. Barlough JE, Madigan JE, Derock E, Dumber JS, Bakken JS. Protection against Ehrlichia equi is conferred by prior infection with the human granulocytic ehrlichia (HGE agent).. J. Clin. Microbiol. 1995;33:3333-3334.
            pmc: PMC228702pubmed: 8586731
          5. Beutler BA, Milsark IW, Cerami A. Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo.. J. Immunol. 1985;135:3972-3977.
            pubmed: 2999236
          6. Beutler E, Lichtman MA, Coller BS, Kipps TJ. Williams hematology: examination of the blood, p. 8-15; comparative hematology, p. 77-85.. 1995.
          7. Chang Y-F, Novosel V, Dubovi E, Wong SJ, Chu FK, Chang CF, Del Piero F, Shin S, Lein DH. Experimental infection of the human granulocytic ehrlichiosis agent in horses.. Vet. Parasitol. 1998;78:137-145.
            pubmed: 9735918
          8. Chen S-M, Dumler JS, Bakken JS, Walker DH. Identification of a granulocytotropic Ehrlichia species as the etiologic agent of human disease.. J. Clin. Microbiol. 1994;32:589-595.
            pmc: PMC263091pubmed: 8195363
          9. Dumler JS, Trigiani ER, Bakken JS, Aguero-Rosenfeld ME, Wormser GP. Serum cytokine responses during acute human granulocytic ehrlichiosis.. Clin. Diagn. Lab. Immunol. 2000;7:6-8.
            pmc: PMC95813pubmed: 10618268
          10. Franchini M, Gilli U, Akens MK, Fellenberg RV, Bracher V. The role of neutrophil chemotactic cytokines in the pathogenesis of equine chronic obstructive pulmonary disease (COPD).. Vet. Immunol. Immunopathol. 1998;66:52-65.
            pubmed: 9847020
          11. Giguere S, Prescott JF. Quantitation of equine cytokine mRNA expression by reverse transcription-competitive polymerase chain reaction.. Vet. Immunol. Immunopathol. 1999;67:1-15.
            pubmed: 9950350
          12. Hodzic E, Fish D, Maretzki CM, De Silva AM, Feng S, Barthold SW. Acquisition and transmission of the agent of human granulocytic ehrlichiosis by Ixodes scapularis ticks.. J. Clin. Microbiol. 1998;36:3574-3578.
            pmc: PMC105242pubmed: 9817875
          13. Jahangir A, Kolbert C, Edwards W, Mitchell P, Dumler JS, Persing DH. Fatal pancarditis associated with human granulocytic ehrlichiosis in a 44-year-old man.. Clin. Infect. Dis. 1998;27:1424-1427.
            pubmed: 9868655
          14. Katavolos P, Armstrong PM, Dawson JE, Telford SR. Duration of tick attachment required for transmission of granulocytic ehrlichiosis.. J. Infect. Dis. 1998;177:1422-1425.
            pubmed: 9593039
          15. Kim H-Y, Rikihisa Y. Characterization of monoclonal antibodies to the 44-kilodalton major outer membrane protein of the human granulocytic ehrlichiosis agent.. J. Clin. Microbiol. 1998;36:3278-3284.
            pmc: PMC105315pubmed: 9774579
          16. Kim H-Y, Rikihisa Y. Expression of interleukin-1β, tumor necrosis factor-α, and interleukin-6 in human peripheral blood leukocytes exposed to human granulocytic ehrlichiosis agent or recombinant major surface protein P44.. Infect. Immun. 2000;68:3394-3402.
            pmc: PMC97610pubmed: 10816490
          17. Kim H-Y, Rikihisa Y. Roles of p38 mitogen-activated protein kinase, NF-κB, and protein kinase C in proinflammatory cytokine mRNA expression by human peripheral blood leukocytes in response to Anaplasma phagocytophila.. Infect. Immun. 2002;70:4132-4141.
            pmc: PMC128199pubmed: 12117921
          18. Klein MB, Hu S, Chao CC, Goodman JL. The agent of human granulocytic ehrlichiosis induces the production of myelosuppressing chemokines without induction of proinflammatory cytokines.. J. Infect. Dis. 2000;182:200-205.
            pubmed: 10882598
          19. Kobluk CN, Ames TR, Geor RJ. The horse disease and clinical management: equine gastrointestinal surgery, p. 329-361.. 1995.
          20. Lebech AM, Hansen K, Pancholi P, Sloan LM, Magera JM, Persing DH. Immunoserologic evidence of human granulocytic ehrlichiosis in Danish patients with Lyme neuroborreliosis.. Scand. J. Infect. Dis. 1998;30:173-176.
            pubmed: 9730306
          21. Lepidi H, Bunnell JE, Martin ME, Madigan JE, Stuen S, Dumler JS. Comparative pathology and immunohistology associated with clinical illness after Ehrlichia phagocytophila-group infections.. Am. J. Trop. Med. Hyg. 2000;62:29-37.
            pubmed: 10761721
          22. Lin Q, Zhi N, Ohashi N, Horowitz HW, Aguero-Rosenfeld ME, Raffalli J, Wormser GP, Rikihisa Y. Analysis of sequences and loci of p44 homologs expressed by Anaplasma phagocytophila in acutely infected patients.. J. Clin. Microbiol. 2002;40:2981-2988.
            pmc: PMC120678pubmed: 12149362
          23. Lotric-Furlan S, Avsic-Zupanc T, Petrovec M, Nicholson WL, Sumner JW, Childs JE, Strle F. Clinical and serological follow-up of patients with human granulocytic ehrlichiosis in Slovenia.. Clin. Diagn. Lab. Immunol. 2001;8:899-903.
            pmc: PMC96168pubmed: 11527800
          24. Madigan JE, Barlough JE, Dumler JS, Schankman NS, DeRock E. Equine granulocytic ehrlichiosis in Connecticut caused by an agent resembling the human granulocytotropic ehrlichia.. J. Clin. Microbiol. 1996;34:434-435.
            pmc: PMC228814pubmed: 8789032
          25. Madigan JE, Richter PJ, Kimsey RB, Barlough JE, Bakken JS, Dumler JS. Transmission and passage in horses of the agent of human granulocytic ehrlichiosis.. J. Infect. Dis. 1995;172:1141-1144.
            pubmed: 7561199
          26. Massung RF, Owens JH, Ross D, Reed KD, Petrovec M, Bjoersdorff A, Coughlin RT, Beltz GA, Murphy C. Sequence analysis of the ank gene of granulocytic ehrlichiae.. J. Clin. Microbiol. 2000;38:2917-2922.
            pmc: PMC87147pubmed: 10921951
          27. McQuiston JH, Paddock CD, Holman RC, Childs JE. The human ehrlichioses in the United States.. Emerg. Infect. Dis. 1999;5:635-642.
            pmc: PMC2627718pubmed: 10511519
          28. Morris DD. Endotoxemia in horses: a review of cellular and humoral mediators involved in its pathogenesis.. J. Vet. Intern. Med. 1991;5:167-181.
            pubmed: 1920254
          29. Pancholi P, Kolbert CP, Mitchell PD, Reed KD, Dumler JS, Bakken JS, Telford SR, Persing DH. Ixodes dammini as a potential vector of human granulocytic ehrlichiosis.. J. Infect. Dis. 1995;172:1007-1012.
            pubmed: 7561173
          30. Petrovec M, Lotric-Furlan S, Avsic-Zupanc T, Strle F, Brouqui P, Roux V, Dumler JS. Human disease in Europe caused by a granulocytic Ehrlichia species.. J. Clin. Microbiol. 1997;35:1556-1559.
            pmc: PMC229786pubmed: 9163481
          31. Pusterla N, Madigan JE, Asanovich KM, Chae JS, Derock E, Leutenegger CM, Pusterla JB, Lutz H, Dumler JS. Experimental inoculation with human granulocytic ehrlichia agent derived from high- and low-passage cell culture in horses.. J. Clin. Microbiol. 2000;38:1276-1278.
            pmc: PMC88606pubmed: 10699041
          32. Pusterla N, Leutenegger CM, Chae J-S, Lutz H, Kimsey RB, Dumler JS, Madigan JE. Quantitative evaluation of ehrlichial burden in horses after experimental transmission of human granulocytic ehrlichia agent by intravenous inoculation with infected leukocytes and by infected ticks.. J. Clin. Microbiol. 1999;37:4042-4044.
            pmc: PMC85876pubmed: 10565928
          33. Rikihisa Y, Zhi N, Wormser GP, Wen B, Horowitz HW, Hechemy KE. Ultrastructural and antigenic characterization of a granulocytic ehrlichiosis agent directly isolated and stably cultivated from a patient in New York State.. J. Infect. Dis. 1997;175:210-213.
            pubmed: 8985223
          34. Telford SR, Dawson JE, Katavolos P, Warner CK, Kolbert CP, Persing DH. Perpetuation of the agent of human granulocytic ehrlichiosis in a deer tick-rodent cycle.. Proc. Natl. Acad. Sci. USA 1996;93:6209-6214.
            pmc: PMC39215pubmed: 8650245
          35. Thomas V, Anguita J, Barthold SW, Fikrig E. Coinfection with Borrelia burgdorferi and the agent of human granulocytic ehrlichiosis alters murine immune responses, pathogen burden, and severity of Lyme arthritis.. Infect. Immun. 2001;69:3359-3371.
            pmc: PMC98295pubmed: 11292759
          36. Zhi N, Ohashi N, Rikihisa Y. Multiple p44 genes encoding major outer membrane proteins are expressed in the human granulocytic ehrlichiosis agent.. J. Biol. Chem. 1999;274:17828-17836.
            pubmed: 10364227
          37. Zhi N, Ohashi N, Tajima T, Mott J, Stich RW, Grover D, Telford SR, Lin Q, Rikihisa Y. Transcript heterogeneity of p44 multigene family in human granulocytic ehrlichiosis agent transmitted by ticks.. Infect. Immun. 2002;70:1175-1184.
            pmc: PMC127761pubmed: 11854198
          Subscribe to our newsletter
          Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.