Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Role of Interleukin-4 (IL-4) in Respiratory Infection and Allergy Caused by Early-Life Chlamydia Infection

  • Li, Shujun (Department of Clinical Laboratory, People's Hospital of Xing'an League) ;
  • Wang, Lijuan (Department of Five Sense Organs, People's Hospital of Xing'an League) ;
  • Zhang, Yulong (Department of Clinical Laboratory, People's Hospital of Xing'an League) ;
  • Ma, Long (Department of Clinical Laboratory, People's Hospital of Xing'an League) ;
  • Zhang, Jing (Department of Clinical Laboratory, People's Hospital of Xing'an League) ;
  • Zu, Jianbing (Department of Clinical Laboratory, People's Hospital of Xing'an League) ;
  • Wu, Xuecheng (Department of Clinical Laboratory, Shenzhen People's Hospital)
  • Received : 2021.04.21
  • Accepted : 2021.06.26
  • Published : 2021.08.28
Download PDF
⟨ Previous Next ⟩

Abstract

Chlamydia pneumoniae is a type of pathogenic gram-negative bacteria that causes various respiratory tract infections including asthma. Chlamydia species infect humans and cause respiratory infection by rupturing the lining of the respiratory which includes the throat, lungs and windpipe. Meanwhile, the function of interleukin-4 (IL-4) in Ch. pneumoniae respiratory infection and its association with the development of airway hyperresponsiveness (AHR) in adulthood and causing allergic airway disease (AAD) are not understood properly. We therefore investigated the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. In this study, Ch. pneumonia strain was propagated and cultured in HEp-2 cells according to standard protocol and infant C57BL/6 mice around 3-4 weeks old were infected to study the role of IL-4 in respiratory infection and allergy caused by early life Chlamydia infection. We observed that IL-4 is linked with Chlamydia respiratory infection and its absence lowers respiratory infection. IL-4R α2 is also responsible for controlling the IL-4 signaling pathway and averts the progression of infection and inflammation. Furthermore, the IL-4 signaling pathway also influences infection-induced AHR and aids in increasing AAD severity. STAT6 also promotes respiratory infection caused by Ch. pneumoniae and further enhanced its downstream process. Our study concluded that IL-4 is a potential target for preventing infection-induced AHR and severe asthma.

Keywords

References

  1. Chow AW, Hall CB, Klein JO, Kammer RB, Meyer R, J S Remington. 1992. Evaluation of new anti-infective drugs for the treatment of respiratory tract infections. Infectious Diseases Society of America and the Food and Drug Administration. Clin. Infect. Dis. 15: S62-88.
  2. Miguel RDV, Harvey SA, LaFramboise WA, Reighard SD, Matthews DB, T L Cherpes. 2013. Human female genital tract infection by the obligate intracellular bacterium Chlamydia trachomatis elicits robust Type 2 immunity. PLoS One 8: e58565. https://doi.org/10.1371/journal.pone.0058565
  3. Stokes HS, Martens JM, Walder K, Segal Y, Berg ML, A TD Bennett. 2020. Species, sex and geographic variation in Chlamydial prevalence in abundant wild Australian parrots. Sci. Rep. 10: 20478. https://doi.org/10.1038/s41598-020-77500-5
  4. Stokes HS, Martens JM, Jelocnik M, Walder K, Segal Y, M L Berg, et al. 2020. Chlamydial diversity and predictors of infection in a wild Australian parrot, the Crimson Rosella (Platycercus elegans). Transbound Emerg. Dis. 68: 487-498.
  5. Butcher R, Sokana O, Jack K, Sui L, Russell C, A Last, et al. 2018. Clinical signs of trachoma are prevalent among Solomon Islanders who have no persistent markers of prior infection with Chlamydia trachomatis. Wellcome Open Res. 3: 14. https://doi.org/10.12688/wellcomeopenres.13423.2
  6. Butcher R, Handley B, Garae M, Taoaba R, Pickering H, Bong A, et al. 2020. Ocular Chlamydia trachomatis infection, anti-Pgp3 antibodies and conjunctival scarring in Vanuatu and Tarawa, Kiribati before antibiotic treatment for trachoma. J. Infect. 80: 454-461. https://doi.org/10.1016/j.jinf.2020.01.015
  7. Ramadhani AM, Derrick T, Macleod D, Holland MJ, Burton MJ. 2016. The relationship between active trachoma and ocular Chlamydia trachomatis infection before and after mass antibiotic treatment. PLoS Negl. Trop. Dis. 10: e0005080. https://doi.org/10.1371/journal.pntd.0005080
  8. Lee JS, Munoz BE, Mkocha H, Gaydos CA, Quinn TC, West SK. 2014. The effect of multiple rounds of mass drug administration on the association between ocular Chlamydia trachomatis infection and follicular trachoma in preschool-aged children. PLoS Negl. Trop. Dis. 8: e2761. https://doi.org/10.1371/journal.pntd.0002761
  9. Razali N, Hohjoh H, Inazumi T, Maharjan BD, Nakagawa K, Konishi M, et al. 2020. Induced prostanoid synthesis regulates the balance between Th1- and Th2-producing inflammatory cytokines in the thymus of diet-restricted mice. Biol. Pharm. Bull 43: 649-662. https://doi.org/10.1248/bpb.b19-00838
  10. von Mutius E, Smits HH. 2020. Primary prevention of asthma: from risk and protective factors to targeted strategies for prevention. Lancet 396: 854-866. https://doi.org/10.1016/S0140-6736(20)31861-4
  11. Zhou F, Liu P, Lv H, Gao Z, Chang W, Xu Y. 2021. miR-31 attenuates murine allergic rhinitis by suppressing interleukin-13-induced nasal epithelial inflammatory responses. Mol. Med. Rep. 23: 42-51.
  12. Furue M. 2020. Regulation of skin barrier function via competition between AHR axis versus IL-13/IL-4-JAK-STAT6/STAT3 axis: pathogenic and therapeutic implications in atopic dermatitis. J. Clin. Med. 9: 3741-3749. https://doi.org/10.3390/jcm9113741
  13. Furue M. 2020. Regulation of filaggrin, loricrin, and involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: pathogenic implications in atopic dermatitis. Int. J. Mol. Sci. 21: 5382-5391. https://doi.org/10.3390/ijms21155382
  14. Snodgrass RG, Benatzy Y, Schmid T, Namgaladze D, Mainka M, Schebb NH, et al. 2021. Efferocytosis potentiates the expression of arachidonate 15-lipoxygenase (ALOX15) in alternatively activated human macrophages through LXR activation. Cell Death Differ. 28: 1301-1316. https://doi.org/10.1038/s41418-020-00652-4
  15. Mandlik DS, Mandlik SK. 2020. New perspectives in bronchial asthma: pathological, immunological alterations, biological targets, and pharmacotherapy. Immunopharmacol. Immunotoxicol. 42: 521-544. https://doi.org/10.1080/08923973.2020.1824238
  16. Horvat JC, Starkey MR, Kim RY, Phipps S, Gibson PG, Beagley KW, et al. 2010. Early-life chlamydial lung infection enhances allergic airways disease through age-dependent differences in immunopathology. J. Allergy Clin. Immunol. 125: 617-625. https://doi.org/10.1016/j.jaci.2009.10.018
  17. Kaiko GE, Phipps S, Hickey DK, Lam CE, Hansbro PM, Foster PS, et al. 2008. Chlamydiamuridarum infection subverts dendritic cell function to promote Th2 immunity and airways hyperreactivity. J. Immunol. 180: 2225-2232. https://doi.org/10.4049/jimmunol.180.4.2225
  18. Jupelli M, Guentzel MN, Meier PA, Zhong G, Murthy AK, Arulanandam BP. 2008. Endogenous IFN-gamma production is induced and required for protective immunity against pulmonary chlamydial infection in neonatal mice. J. Immunol. 180: 4148-4155. https://doi.org/10.4049/jimmunol.180.6.4148
  19. Gnarpe J, Gnarpe H, Sundelof B. 1991. Endemic prevalence of Chlamydia pneumoniae in subjectively healthy persons. Scand. J. Infect. Dis. 23: 387-398. https://doi.org/10.3109/00365549109024328
  20. Schmidt SM, Muller CE, Mahner B, Wiersbitzky SK. 2002. Prevalence, rate of persistence and respiratory tract symptoms of Chlamydia pneumoniae infection in 1211 kindergarten and school age children. Pediatr. Infect. Dis. J. 21: 758-762. https://doi.org/10.1097/00006454-200208000-00012
  21. Hansbro PM, Starkey MR, Kim RY, Stevens RL, Foster PS, Horvat JC. 2012. Programming of the lung by early-life infection. J. Dev. Orig. Health Dis. 3: 153-158. https://doi.org/10.1017/S2040174412000050
  22. Finkelman FD, Katona IM, Urban JF Jr, Holmes J, Ohara J, Tung AS. 1988. IL-4 is required to generate and sustain in vivo IgE responses. J. Immunol. 141: 2335-2341.
  23. Madden KB, Urban JF Jr, Ziltener HJ, Schrader JW, Finkelman FD, Katona IM. 1991. Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis. J. Immunol. 147: 1387-1391.
  24. Temann UA, Prasad B, Gallup MW, Basbaum C, Ho SB, Flavell RA, et al. 1997. A novel role for murine IL-4 in vivo: induction of MUC5AC gene expression and mucin hypersecretion. Am. J. Respir. Cell Mol. Biol. 16: 471-478. https://doi.org/10.1165/ajrcmb.16.4.9115759
  25. Hogan SP, Mould A, Kikutani H, Ramsay AJ, Foster PS. 1997. Aeroallergen-induced eosinophilic inflammation, lung damage, and airways hyperreactivity in mice can occur independently of IL-4 and allergen-specific immunoglobulins. J. Clin. Invest. 99: 1329-1339. https://doi.org/10.1172/JCI119292
  26. Porritt RA, Crother TR. 2016. Chlamydia pneumoniae infection and inflammatory diseases. For. Immunopathol. Dis. Therap. 7: 237-254. https://doi.org/10.1615/ForumImmunDisTher.2017020161
  27. Hahn DL, Azenabor AA, Beatty WL, Byrne GI. 2002. Chlamydia pneumoniae as a respiratory pathogen. Front. Biosci. 7: e66-76. https://doi.org/10.2741/hahn
  28. Cheok YY, Lee CYQ, Cheong HC, Looi CY, Wong WF. 2020. Chronic inflammatory diseases at secondary sites ensuing urogenital or pulmonary Chlamydia Infections. Microorganisms 8: 127-132. https://doi.org/10.3390/microorganisms8010127
  29. Jolly AL, Rau S, Chadha AK, Abdulraheem EA, Dean D. 2019. Stromal fibroblasts drive host inflammatory responses that are dependent on Chlamydia trachomatis strain type and likely influence disease outcomes. mBio 10: e00225-00239.
  30. Kalman S, Mitchell W, Marathe R, Lammel C, Fan J, Hyman RW, et al. 1999. Comparative genomes of Chlamydia pneumoniae and C. trachomatis. Nat. Genet. 21: 385-389. https://doi.org/10.1038/7716
  31. Belay T, Martin E, Brown G, Crenshaw R, Street J, Freem A, et al. 2020. Modulation of T helper 1 and T helper 2 immune balance in a murine stress model during Chlamydia muridarum genital infection. PLoS One 15: e0226539. https://doi.org/10.1371/journal.pone.0226539
  32. Kaiko GE, Phipps S, Hickey DK, Lam CE, Hansbro PM, Foster PS, et al. 2008. Chlamydia muridarum infection subverts dendritic cell function to promote Th2 immunity and airways hyperreactivity. J. Immunol. 180: 2225-2232. https://doi.org/10.4049/jimmunol.180.4.2225
  33. Yang X. 2003. Role of cytokines in Chlamydia trachomatis protective immunity and immunopathology. Curr. Pharm. Des. 9: 67-73. https://doi.org/10.2174/1381612033392486