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Chlamydophila pneumoniae re-infection triggers the production of IL-17A and IL-17E, important regulators of airway inflammation

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Abstract

Objective

Investigation of the effects of interleukin (IL)-17 cytokines in Chlamydophila pneumoniae-infected mice.

Methods

Mice were infected with C. pneumoniae once or three times and the expression of IL-17 cytokines was followed by RT qPCR from day 1 to day 28 after infection and re-infection. After the treatment of mice with anti-IL-17A, ELISA was used to detect the differences in cytokine and chemokine production. The number and phenotype of the IL-17A-producing cells were determined by ELISPOT.

Results

Chlamydophila pneumoniae induced IL-17A and IL-17F from day 2 after infection, and their levels remained elevated on day 28. The expression of IL-17C, IL-17D and IL-17E mRNA did not change significantly in response to a single infection. The in vivo neutralization of IL-17A resulted in a higher C. pneumoniae burden in the mouse lungs, a decreased cell influx, and diminished chemokine levels. The phenotype of IL-17A-producing cells was CD4+. The re-infection of mice led to an increased expression of IL-17E mRNA.

Conclusion

These results facilitate an understanding of the early inflammatory response after C. pneumoniae infection and suggest that C. pneumoniae re-infection induces the production of a high amount of IL-17E, which has an important role in the pathogenesis of allergic pulmonary diseases.

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References

  1. Kuo CC, Jackson LA, Campbell LA, Grayston JT. Chlamydia pneumoniae (TWAR). Clin Microbiol Rev. 1995;8:451–61.

    PubMed  CAS  Google Scholar 

  2. Kauppinen M, Saikku P. Pneumonia due to Chlamydia pneumoniae: prevalence, clinical features, diagnosis, and treatment. Clin Infect Dis. 1995;21(Suppl 3):S244–52.

    Article  PubMed  Google Scholar 

  3. Blasi F, Tarsia P, Aliberti S. Chlamydophila pneumoniae. Clin Microbiol Infect. 2009;15:29–35.

    Article  PubMed  CAS  Google Scholar 

  4. Lieberman D, Ben-Yaakov M, Lazarovich Z, Hoffman S, Ohana B, Friedman MG, et al. Infectious etiologies in acute exacerbation of COPD. Diagn Microbiol Infect Dis. 2001;40:95–102.

    Article  PubMed  CAS  Google Scholar 

  5. Beatty WL, Morrison RP, Byrne GI. Persistent chlamydiae: from cell culture to a paradigm for chlamydial pathogenesis. Microbiol Rev. 1994;58:686–99.

    PubMed  CAS  Google Scholar 

  6. Beatty WL, Byrne GI, Morrison RP. Morphologic and antigenic characterization of interferon gamma-mediated persistent Chlamydia trachomatis infection in vitro. Proc Natl Acad Sci USA. 1993;90:3998–4002.

    Article  PubMed  CAS  Google Scholar 

  7. Shi Y, Yin J, Zhan H, Feng G, Zhang X, Su X, et al. The pathogenesis of Chlamydia pneumoniae-type pneumonitis in mice. Chin Med J. 2003;116:328–32.

    PubMed  Google Scholar 

  8. Aggarwal S, Ghilardi N, Xie MH, de Sauvage FJ, Gurney AL. Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17. J Biol Chem. 2003;278:1910–4.

    Article  PubMed  CAS  Google Scholar 

  9. Happel KI, Dubin PJ, Zheng M, Ghilardi N, Lockhart C, Quinton LJ, et al. Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J Exp Med. 2005;202:761–9.

    Article  PubMed  CAS  Google Scholar 

  10. Park SJ, Lee YC. Interleukin-17 regulation: an attractive therapeutic approach for asthma. Respir Res. 2010;11:78.

    Article  PubMed  Google Scholar 

  11. Wilson RH, Whitehead GS, Nakano H, Free ME, Kolls JK, Cook DN. Allergic sensitization through the airway primes Th17-dependent neutrophilia and airway hyperresponsiveness. Am J Respir Crit Care Med. 2009;180:720–30.

    Article  PubMed  CAS  Google Scholar 

  12. Zhang X, Gao L, Lei L, Zhong Y, Dube P, Berton MT, et al. A MyD88-dependent early IL-17 production protects mice against airway infection with the obligate intracellular pathogen Chlamydia muridarum. J Immunol. 2009;183:1291–300.

    Article  PubMed  CAS  Google Scholar 

  13. Fort MM, Cheung J, Yen D, Li J, Zurawski SM, Lo S, et al. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity. 2001;15:985–95.

    Article  PubMed  CAS  Google Scholar 

  14. Lee J, Ho WH, Maruoka M, Corpuz RT, Baldwin DT, Foster JS, et al. IL-17E, a novel proinflammatory ligand for the IL-17 receptor homolog IL-17Rh1. J Biol Chem. 2001;276:1660–4.

    Article  PubMed  CAS  Google Scholar 

  15. Fallon PG, Ballantyne SJ, Mangan NE, Barlow JL, Dasvarma A, Hewett DR, et al. Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J Exp Med. 2006;203:1105–16.

    Article  PubMed  CAS  Google Scholar 

  16. Kim M, Manoukian R, Yeh R, Silbiger S, Danilenko D, Scully S, et al. Transgenic overexpression of human IL-17E results in eosinophilia, B-lymphocyte hyperplasia, and altered antibody production. Blood. 2002;100:2330–40.

    Article  PubMed  CAS  Google Scholar 

  17. Zhou X, Chen Q, Moore J, Kolls J, Halperin S, Wang J. Critical role of the interleukin-17/interleukin-17 receptor axis in regulating host susceptibility to respiratory infection with Chlamydia species. Infect Immun. 2009;77:5059–70.

    Article  PubMed  CAS  Google Scholar 

  18. Bai H, Cheng J, Gao X, Joyee AG, Fan Y, Wang S, et al. IL-17/Th17 promotes type 1 T cell immunity against pulmonary intracellular bacterial infection through modulating dendritic cell function. J Immunol. 2009;183:5886–95.

    Article  PubMed  CAS  Google Scholar 

  19. Horvat JC, Starkey MR, Kim RY, Beagley KW, Preston JA, Gibson PG, et al. Chlamydial respiratory infection during allergen sensitization drives neutrophilic allergic airways disease. J Immunol. 2010;184:4159–69.

    Article  PubMed  CAS  Google Scholar 

  20. Burián K, Hegyesi H, Buzás E, Endrész V, Kis Z, Falus A, et al. Chlamydophila (Chlamydia) pneumoniae induces histidine decarboxylase production in the mouse lung. Immunol Lett. 2003;89:229–36.

    Article  PubMed  Google Scholar 

  21. Kis Z, Burian K, Treso B, Acs K, Prohaszka Z, Fust G, et al. Inflammatory- and immune responses in relation to bacterial replication in mice following re-infections with Chlamydophila pneumoniae. Inflamm Res. 2008;57:287–95.

    Article  PubMed  CAS  Google Scholar 

  22. Johnston SL, Martin RJ. Chlamydophila pneumoniae and Mycoplasma pneumoniae: a role in asthma pathogenesis? Am J Respir Crit Care Med. 2005;172:1078–89.

    Article  PubMed  Google Scholar 

  23. Angkasekwinai P, Park H, Wang Y, Chang S, Corry D, Liu Y, et al. Interleukin 25 promotes the initiation of proallergic type 2 responses. J Exp Med. 2007;204:1509–17.

    Article  PubMed  CAS  Google Scholar 

  24. Iwakura Y, Nakae S, Saijo S, Ishigame H. The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol Rev. 2008;226:57–79.

    Article  PubMed  CAS  Google Scholar 

  25. Khader SA, Pearl JE, Sakamoto K, Gilmartin L, Bell GK, Jelley-Gibbs DM, et al. IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. J Immunol. 2005;175:788–95.

    PubMed  CAS  Google Scholar 

  26. Okamoto Yoshida Y, Umemura M, Yahagi A, O’Brien RL, Ikuta K, Kishihara K, et al. Essential role of IL-17A in the formation of a mycobacterial infection-induced granuloma in the lung. J Immunol. 2010; 184:4414–22.

    Google Scholar 

  27. Schulz SM, Köhler G, Schütze N, Knauer J, Straubinger RK, Chackerian AA, et al. Protective immunity to systemic infection with attenuated Salmonella enterica serovar enteritidis in the absence of IL-12 is associated with IL-23-dependent IL-22, but not IL-17. J Immunol. 2008;181:7891–901.

    PubMed  CAS  Google Scholar 

  28. Raffatellu M, Santos RL, Verhoeven DE, George MD, Wilson RP, Winter SE, et al. Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med. 2008;14:421–8.

    Article  PubMed  CAS  Google Scholar 

  29. Hamada S, Umemura M, Shiono T, Tanaka K, Yahagi A, Begum M, et al. IL-17A produced by gamma delta T cells plays a critical role in innate immunity against Listeria monocytogenes infection in the liver. Journal of Immunology. 2008;181:3456–63.

    CAS  Google Scholar 

  30. Ye P, Garvey P, Zhang P, Nelson S, Bagby G, Summer W, et al. Interleukin-17 and lung host defense against Klebsiella pneumoniae infection. Am J Respir Cell Mol Biol. 2001;25:335–40.

    Article  PubMed  CAS  Google Scholar 

  31. McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity. 2008;28:445–53.

    Article  PubMed  CAS  Google Scholar 

  32. Lockhart E, Green AM, Flynn JL. IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J Immunol. 2006;177:4662–9.

    PubMed  CAS  Google Scholar 

  33. Umemura M, Yahagi A, Hamada S, Begum MD, Watanabe H, Kawakami K, et al. IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. J Immunol. 2007;178:3786–96.

    PubMed  CAS  Google Scholar 

  34. Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010;10:479–89.

    Article  PubMed  CAS  Google Scholar 

  35. Morrison RP. Chlamydial hsp60 and the immunopathogenesis of chlamydial disease. Semin Immunol. 1991;3:25–33.

    PubMed  CAS  Google Scholar 

  36. Kaukoranta-Tolvanen SS, Laurila AL, Saikku P, Leinonen M, Liesirova L, Laitinen K. Experimental infection of Chlamydia pneumoniae in mice. Microb Pathog. 1993;15:293–302.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Zsótér Gizella and Lévai Istvánné for excellent technical support. This work was supported by OTKA National Research Fund Grant PD 100442, and Grants TÁMOP-4.2.1./B-09/1/KONV-2010-0005, and TÁMOP-4.2.2./B-2013 from the New Széchenyi Plan.

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Correspondence to Katalin Burián.

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Responsible Editor: Andras Falus.

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Mosolygó, T., Korcsik, J., Balogh, E.P. et al. Chlamydophila pneumoniae re-infection triggers the production of IL-17A and IL-17E, important regulators of airway inflammation. Inflamm. Res. 62, 451–460 (2013). https://doi.org/10.1007/s00011-013-0596-1

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  • DOI: https://doi.org/10.1007/s00011-013-0596-1

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