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Mycoplasma pneumoniae Extract Induces an IL-17-Associated Inflammatory Reaction in Murine Lung: Implication for Mycoplasmal Pneumonia

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Abstract

Mycoplasma pneumoniae (Mp) may cause immune cell reactions as pivotal aspects of this clinically common respiratory pathogen. Our aim is to determine if Mp extract induces a cellular immune response associated with interleukin (IL)-17, leading to lung inflammation and lung injury. BALB/c mice were immunized with Mp extract intraperitoneally followed by its intratracheal administration, to mimic repeated Mp infection found in humans (repeated inoculation, RI group). Those with a single inoculation were compared as single inoculation group (SI group). Analysis of bronchoalveolar lavage fluid (BALF) demonstrated that keratinocyte-derived cytokine, tumor necrosis factor-α, and IL-6 were produced and peaked on days 0.5 or 1, followed by IL-17 on day 2. Levels of these mediators in BALF were higher in RI group than SI group (P < 0.05). Further, significantly more neutrophils were recruited to the lungs of the RI group (P < 0.05). These observations suggest that IL-17 is involved in the prolonged induction of neutrophils in mice treated with Mp extract.

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References

  1. Waite, K.B., and D.F. Talkington. 2004. Mycoplasma pneumoniae and its role as a human pathogen. Clinical Microbiology Reviews 17: 697–728.

    Article  Google Scholar 

  2. Matsuoka, M., M. Narita, N. Okazaki, H. Ohya, T. Yamazaki, K. Ouchi, I. Suzuki, T. Andoh, T. Kenri, Y. Sasaki, A. Horino, M. Shintani, Y. Arakawa, and T. Sasaki. 2004. Characterization and molecular analysis of macrolide-resistant Mycoplasma pneumoniae clinical obtained in Japan. Antimicrobial Agents and Chemotherapy 48: 4624–4630.

    Article  PubMed  CAS  Google Scholar 

  3. Opitz, O., K. Pietsch, S. Ehlers, and E. Jacobs. 1996–1997. Cytokine gene expression in immune mice reinfected with Mycoplasma pneumoniae: the role of T cell subsets in aggravating the inflammatory response. Immunobiology 196: 575–587.

    Article  Google Scholar 

  4. British Thoracic Society Standards of Care Committee. 2002. BTS guidelines for the management of community acquired pneumonia in children. Thorax 57(Supple1): i1–i24.

    Google Scholar 

  5. Fernald, G.W., A.M. Collier, and W.A. Clyde Jr. 1975. Respiratory infections due to Mycoplasma pneumoniae in infants and children. Pediatrics 55: 327–335.

    PubMed  CAS  Google Scholar 

  6. Lim, W.S., S.V. Baudouin, R.C. George, A.T. Hill, C. Jamieson, I. Le Jeune, J.T. Macfarlane, R.C. Read, H.J. Roberts, M.L. Levy, M. Wani, M.A. Woodhead; Pneumonia Guidelines Committee of the BTS Standards of Care Committee. 2009. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax 64(Suppl 3): iii1–55.

    Article  Google Scholar 

  7. Steohen, G.B. Mycoplasma pneumoniae and atypical pneumonia In: Mandell, Douglas and Bennett's principle and principles and practice of infectious diseases. G.L. Mandell, J.E. Bennett, R. Dolin, editors. Philadelphia: Elsevier Inc., 2010: 2481–2489

  8. Smith, C.B., W.T. Friedewald, and R.M. Chanock. 1967. Inactivated Mycoplasma pneumoniae vaccine. Evaluation in volunteers. The Journal of the American Medical Association 199: 353–358.

    Article  CAS  Google Scholar 

  9. Koh, Y.Y., Y. Park, H.J. Lee, and C.K. Kim. 2001. Levels of interleukin-2, interferon-γ, and interleukin-4 in bronchoalveolar lavage fluid from patients with Mycoplasma pneumonia: implication of tendency toward increased immunoglobulin E production. Pediatrics 107: E39.

    Article  PubMed  CAS  Google Scholar 

  10. Nisar, N., R. Guleria, S. Kumar, T.C. Chawla, and N.R. Biswas. 2007. Mycoplasma pneumoniae and its role in asthma. Postgraduate Medical Journal 83: 100–104.

    Article  CAS  Google Scholar 

  11. Lee, K.Y., H.S. Lee, J.H. Hong, M.H. Lee, J.S. Lee, D. Burgner, and B.C. Lee. 2006. Role of prednisolone treatment in severe Mycoplasma pneumoniae pneumonia in children. Pediatric Pulmonology 41: 263–268.

    Article  PubMed  Google Scholar 

  12. Radisic, M., A. Torn, P. Gutierrez, H.A. Defranchi, and P. Pardo. 2000. Severe acute lung injury caused by Mycoplasma pneumoniae: potential role for steroid pulses in treatment. Clinical Infectious Diseases 31: 1507–1511.

    Article  PubMed  CAS  Google Scholar 

  13. Hirao, S., H. Wada, K. Nakagaki, T. Saraya, D. Kurai, S. Mikura, T. Yasutake, M. Higaki, T. Yokoyama, H. Ishii, K. Nakata, T. Aakashi, S. Kamiya, and H. Goto. 2011. Inflammation provoked by Mycoplasma pneumoniae extract: implications for combination treatment with clarithromycin and dexamethasone. FEMS Immunology and Medical Microbiology 62: 182–189.

    Article  PubMed  CAS  Google Scholar 

  14. Saraya, T., K. Nakata, K. Nakagaki, N. Motoi, K. Iihara, Y. Fujioka, T. Oka, D. Kurai, H. Wada, H. Ishii, H. Taguchi, S. Kamiya, and H. Goto. 2011. Identification of a mechanism for lung inflammation caused by Mycoplasma pneumoniae using a novel mouse model. Results in Immunology 1: 76–87.

    Article  CAS  Google Scholar 

  15. Wu, Q., R.J. Martin, J.G. Rino, R. Breed, R.M. Torres, and H.W. Chu. 2007. IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection. Microbes and Infection 9: 78–86.

    Article  PubMed  CAS  Google Scholar 

  16. Michelow, I.C., K. Katz, G.H. McCracken, and R.D. Hardy. 2007. Systemic cytokine profile in children with community-acquired pneumonia. Pediatric Pulmonology 42: 640–645.

    Article  PubMed  Google Scholar 

  17. Pridgeon, C., L. Bugeon, L. Donnelly, U. Straschil, S.J. Tudhope, P. Fenwick, J.R. Lamb, P.J. Barnes, and M.J. Dallman. 2011. Regulation of IL-17 in chronic inflammation in the human lung. Clinical Science 120: 515–524.

    Article  PubMed  Google Scholar 

  18. Vanaudenaerde, B.M., S.E. Verleden, R. De, S.I. Vos, A. Vleeschauwer, R. Willems-Widyastuti, D.E.Van Geenens, L.J. Raemdonck, E.K. Dupont, and I.Meyts Verbeken. 2011. Innate and adaptive interleukin-17-producing lymphocytes in chronic inflammatory lung disorders. American Journal of Respiratory and Critical Care Medicine 183: 977–986.

    Article  PubMed  CAS  Google Scholar 

  19. Bettelli, E., T. Korn, M. Oukka, and V.K. Kuchroo. 2008. Induction and effector functions of T(H)17 cells. Nature 453: 1051–1057.

    Article  PubMed  CAS  Google Scholar 

  20. Mills, K.H. 2008. Induction, function and regulation of IL-17-producing T cells. European Journal of Immunology 38: 2636–2649.

    Article  PubMed  CAS  Google Scholar 

  21. Shen, N., J. Wang, M. Zhao, F. Pei, and B. He. 2011. Anti-interleukin-17 antibodies attenuate airway inflammation in tobacco-smoke-exposed mice. Inhal Toxicol 23: 212–218.

    Article  PubMed  CAS  Google Scholar 

  22. Chmura, K., X. Bai, M. Nakamura, P. Kandasamy, M. McGibney, K. Kuronuma, H. Mitsuzawa, D.R. Voelker, and E.D. Chan. 2008. Induction of IL-8 by Mycoplasma pneumoniae membrane in BEAS-2B cells. American Journal of Physiology - Lung Cellular and Molecular Physiology 295: L220–L230.

    Article  PubMed  CAS  Google Scholar 

  23. Sohn, M.H., K.E. Lee, S.Y. Choi, B.C. Kwon, M.W. Chang, and K.E. Kim. 2005. Effect of Mycoplasma pneumoniae lysate on interleukin-8 gene expression in human respiratory epithelial cells. Chest 128: 322–326.

    Article  PubMed  CAS  Google Scholar 

  24. Ferretti, S., O. Bonneau, G.R. Dubois, C.E. Jones, and A. Trifilieff. 2003. IL-17, produced by lymphocytes and neutrophils, is necessary for lipopolysaccharide-induced airway neutrophilia: IL-15 as a possible trigger. The Journal of Immunology 170: 2106–2112.

    PubMed  CAS  Google Scholar 

  25. Hartupee, J., C. Liu, M. Novotny, X. Li, and T. Hamilton. 2007. IL-17 enhances chemokine gene expression through mRNA stabilization. The Journal of Immunology 179: 4135–4141.

    PubMed  CAS  Google Scholar 

  26. Chu, H.W., R. Breed, J.G. Rino, R.J. Harbeck, M.R. Sills, and R.J. Martin. 2006. Repeated respiratory Mycoplasma pneumoniae infections in mice: effect of host genetic background. Microbes and Infection 8: 1764–1772.

    Article  PubMed  CAS  Google Scholar 

  27. Fonseca-Aten, M., A.M. Ríos, A. Mejías, S. Chávez-Bueno, K. Katz, A.M. Gomez, G.H. McCracken Jr., and R.D. Hardy. 2005. Mycoplasma pneumoniae induces host-dependent pulmonary inflammation and airway obstruction in mice. American Journal of Physiology - Lung Cellular and Molecular Physiology 32: 201–210.

    CAS  Google Scholar 

  28. Salvatore, C.M., M. Fonseca-Aten, K. Katz-Gaynor, A.M. Gomez, A. Mejias, C. Somers, S. Chavez-Bueno, G.H. McCracken, and R.D. Hardy. 2007. Respiratory tract infection with Mycoplasma pneumoniae in interleukin-12 knockout mice results in improved bacterial clearance and reduced pulmonary inflammation. Infection and Immunity 75: 236–242.

    Article  PubMed  CAS  Google Scholar 

  29. Salvatore, C.M., M. Fonseca-Aten, K. Katz-Gaynor, A.M. Gomez, and R.D. Hardy. 2008. Intranasal interleukin-12 therapy inhibits Mycoplasma pneumoniae clearance and sustains airway obstruction in murine pneumonia. Infection and Immunity 76: 732–738.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This research was partially supported by the Japanese Ministry of Education, Science, Sports and Culture Grants-in-Aid for Scientific Research of 2007, 1959091, and 2009, 21591298.

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Authors and Affiliations

  1. Department of Respiratory Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan

    Daisuke Kurai, Hiroo Wada, Takeshi Saraya, Hajime Takizawa & Hajime Goto

  2. College of Veterinary Medicine, Nippon Veterinary and Life Science University, 1-7-1, Kyonan-cho, Musashino-shi, Tokyo, 180-8602, Japan

    Kazuhide Nakagaki

  3. Department of Infectious Diseases, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan

    Shigeru Kamiya

  4. Department of Pathology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan

    Yasunori Fujioka

  5. Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 1-757 Asahimachi-Dohri, Chuo-ku, Niigata, 951-8520, Japan

    Koh Nakata

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  1. Daisuke Kurai
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Correspondence to Hajime Goto.

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Kurai, D., Nakagaki, K., Wada, H. et al. Mycoplasma pneumoniae Extract Induces an IL-17-Associated Inflammatory Reaction in Murine Lung: Implication for Mycoplasmal Pneumonia. Inflammation 36, 285–293 (2013). https://doi.org/10.1007/s10753-012-9545-3

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