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IL-17A Secreted by Th17 Cells Is Essential for the Host against Streptococcus agalactiae Infections

  • Chen, Jing (College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University) ;
  • Yang, Siyu (College of Life Science and Technology, Heilongjiang Bayi Agricultural University) ;
  • Li, Wanyu (College of Life Science and Technology, Heilongjiang Bayi Agricultural University) ;
  • Yu, Wei (College of Life Science and Technology, Heilongjiang Bayi Agricultural University) ;
  • Fan, Zhaowei (College of Life Science and Technology, Heilongjiang Bayi Agricultural University) ;
  • Wang, Mengyao (College of Life Science and Technology, Heilongjiang Bayi Agricultural University) ;
  • Feng, Zhenyue (College of Life Science and Technology, Heilongjiang Bayi Agricultural University) ;
  • Tong, Chunyu (College of Life Science and Technology, Heilongjiang Bayi Agricultural University) ;
  • Song, Baifen (College of Life Science and Technology, Heilongjiang Bayi Agricultural University) ;
  • Ma, Jinzhu (College of Life Science and Technology, Heilongjiang Bayi Agricultural University) ;
  • Cui, Yudong (College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University)
  • Received : 2021.03.31
  • Accepted : 2021.04.19
  • Published : 2021.05.28

Abstract

Streptococcus agalactiae is an important bacterial pathogen and causative agent of diseases including neonatal sepsis and meningitis, as well as infections in healthy adults and pregnant women. Although antibiotic treatments effectively relieve symptoms, the emergence and transmission of multidrug-resistant strains indicate the need for an effective immunotherapy. Effector T helper (Th) 17 cells are a relatively newly discovered subpopulation of helper CD4+ T lymphocytes, and which, by expressing interleukin (IL)-17A, play crucial roles in host defenses against a variety of pathogens, including bacteria and viruses. However, whether S. agalactiae infection can induce the differentiation of CD4+ T cells into Th17 cells, and whether IL-17A can play an effective role against S. agalactiae infections, are still unclear. In this study, we analyzed the responses of CD4+ T cells and their defensive effects after S. agalactiae infection. The results showed that S. agalactiae infection induces not only the formation of Th1 cells expressing interferon (IFN)-γ, but also the differentiation of mouse splenic CD4+ T cells into Th17 cells, which highly express IL-17A. In addition, the bacterial load of S. agalactiae was significantly increased and decreased in organs as determined by antibody neutralization and IL-17A addition experiments, respectively. The results confirmed that IL-17A is required by the host to defend against S. agalactiae and that it plays an important role in effectively eliminating S. agalactiae. Our findings therefore prompt us to adopt effective methods to regulate the expression of IL-17A as a potent strategy for the prevention and treatment of S. agalactiae infection.

Keywords

Acknowledgement

This work was supported by the Natural Science Foundation of Heilongjiang Province of China (grant no. ZD2016004), the Scientific Research Team Support Plan of Heilongjiang Bayi Agricultural University (grant no. TDJH201810), the Project of Natural Science Fund Joint Guidance of Heilongjiang Province of China (grant no. LH2019C047) and the Start-Up Fund Plan of Studying Abroad Returning National Research (grant no. ZRCLG201905).

References

  1. Raabe VN, Shane AL. 2019. Group B Streptococcus (Streptococcus agalactiae). Microbiol. Spectr. 7: 10.1128/microbiolspec.GPP3-0007-2018.
  2. Rosen GH, Randis TM, Desai PV, Sapra KJ, Ma B, Gajer P, et al. 2017. Group B Streptococcus and the vaginal microbiota. J. Infect. Dis. 216: 744-751. https://doi.org/10.1093/infdis/jix395
  3. Khan MA, Faiz A, Ashshi AM. 2015. Maternal colonization of group B streptococcus: prevalence, associated factors and antimicrobial resistance. Ann. Saudi Med. 35: 423-427. https://doi.org/10.5144/0256-4947.2015.423
  4. Melin P. 2011. Neonatal group B streptococcal disease: from pathogenesis to preventive strategies. Clin. Microbiol. Infect. 17: 1294-1303. https://doi.org/10.1111/j.1469-0691.2011.03576.x
  5. Edmond KM, Kortsalioudaki C, Scott S, Schraf SJ, Zaidi AKM, Cousens S, et al. 2012. Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis. Lancet 379: 547-556. https://doi.org/10.1016/S0140-6736(11)61651-6
  6. Seale AC, Blencowe H, Bianchi-Jassir F, Embleton N, Bassat Q, Ordi J, et al. 2017. Stillbirth with group B Streptococcus disease worldwide: systematic review and meta-analyses. Clin. Infect. Dis. 65(suppl_2): S125-S132. https://doi.org/10.1093/cid/cix585
  7. Pitts SI, Maruthur NM, Langley GE, Pondo T, Shutt KA, Hollick R, et al. 2018. Obesity, diabetes, and the risk of invasive group B Streptococcal disease in nonpregnant adults in the United States. Open Forum Infect. Dis. 5: ofy030. https://doi.org/10.1093/ofid/ofy030
  8. Doran KS, Nizet V. 2004. Molecular pathogenesis of neonatal group B streptococcal infection: no longer in its infancy. Mol. Microbiol. 54: 23-31. https://doi.org/10.1111/j.1365-2958.2004.04266.x
  9. Francois Watkins LK, McGee L, Schrag SJ, Bella B, Jian JH, Pondo T, et al. 2019. Epidemiology of invasive group B Streptococcal infections among nonpregnant adults in the United States. 2008-2016. JAMA Intern. Med.179: 479-488. https://doi.org/10.1001/jamainternmed.2018.7269
  10. Sendi P, Johansson L, Norrby-Teglund A. 2008. Invasive group B Streptococcal disease in non-pregnant adults : a review with emphasis on skin and soft-tissue infections. Infection 36: 100-111. https://doi.org/10.1007/s15010-007-7251-0
  11. Randis TM, Baker JA, Ratner AJ. 2017. Group B Streptococcal infections. Pediatr. Rev. 38: 254-262. https://doi.org/10.1542/pir.2016-0127
  12. Le Doare K, Heath PT. 2013. An overview of global GBS epidemiology. Vaccine 31 Suppl 4: D7-12. https://doi.org/10.1016/j.vaccine.2013.01.009
  13. Mian GF, Godoy DT, Leal CA, Yuhara TY, Costa GM, Figueiredo HCP. 2009. Aspects of the natural history and virulence of S. agalactiae infection in Nile tilapia. Vet. Microbiol. 136: 180-183. https://doi.org/10.1016/j.vetmic.2008.10.016
  14. Elliott JA, Facklam RR, Richter CB. 1990. Whole-cell protein patterns of nonhemolytic group B, type Ib, streptococci isolated from humans, mice, cattle, frogs, and fish. J. Clin. Microbiol. 28: 628-630. https://doi.org/10.1128/jcm.28.3.628-630.1990
  15. Yildirim AO, Lammler C, Weiss R, Kopp P. 2002. Pheno- and genotypic properties of streptococci of serological group B of canine and feline origin. FEMS Microbiol. Lett. 212: 187-192. https://doi.org/10.1111/j.1574-6968.2002.tb11265.x
  16. Hogeveen H, Huijps K, Lam TJ. 2011. Economic aspects of mastitis: new developments. NZ Vet. J. 59: 16-23. https://doi.org/10.1080/00480169.2011.547165
  17. Keefe GP. 1997. Streptococcus agalactiae mastitis: a review. Can. Vet. J. 38: 429-437.
  18. Gao J, Barkema HW, Zhang L, Liu G, Deng Z, Cai L, et al. 2017. Incidence of clinical mastitis and distribution of pathogens on large Chinese dairy farms. J. Dairy Sci. 100: 4797-4806. https://doi.org/10.3168/jds.2016-12334
  19. Manning SD, Springman AC, Million AD, Millton NR, McNamara SE, Somsel PA, et al. 2010. Association of Group B Streptococcus colonization and bovine exposure: a prospective cross-sectional cohort study. PLoS One 5: e8795. https://doi.org/10.1371/journal.pone.0008795
  20. Cobo-Angel CG, Jaramillo-Jaramillo AS, Palacio-Aguilera M, Jurado-Vargas L, Calvo-Villegas EA, Ospina-Loaiza DA, et al. 2019. Potential group B Streptococcus interspecies transmission between cattle and people in Colombian dairy farms. Sci. Rep. 9: 14025. https://doi.org/10.1038/s41598-019-50225-w
  21. Longtin J, Vermeiren C, Shahinas D, Tamber GS, McGeer A, Low DE, et al. 2011. Novel mutations in a patient isolate of Streptococcus agalactiae with reduced penicillin susceptibility emerging after long-term oral suppressive therapy. Antimicrob. Agents Chemother. 55: 2983-2985. https://doi.org/10.1128/AAC.01243-10
  22. Kimura K, Matsubara K, Yamamoto G, Shibayama K, Arakawa Y. 2013. Active screening of group B streptococci with reduced penicillin susceptibility and altered serotype distribution isolated from pregnant women in Kobe, Japan. Jpn. J. Infect. Dis. 66: 158-160. https://doi.org/10.7883/yoken.66.158
  23. Al Sweih N, Mokaddas E, Jamal W, Phillips OA, Rotimi VO. 2005. In vitro activity of linezolid and other antibiotics against Grampositive bacteria from the major teaching hospitals in Kuwait. J. Chemother. 17: 607-613. https://doi.org/10.1179/joc.2005.17.6.607
  24. Teti G, Mancuso G, Tomasello F. 1993. Cytokine appearance and effects of anti-tumor necrosis factor alpha antibodies in a neonatal rat model of group B streptococcal infection. Infect. Immun. 61: 227-235. https://doi.org/10.1128/iai.61.1.227-235.1993
  25. Clarke D, Letendre C, Lecours MP, Lemire P, Galbas T, Thibodeau J, et al. 2016. Group B Streptococcus induces a rbust IFN-gamma response by CD4(+) T cells in an In Vitro and In Vivo model. J. Immunol. Res. 2016: 5290604. https://doi.org/10.1155/2016/5290604
  26. Cusumano V, Mancuso G, Genovese F, Delfino D, Beninati E, Losi E, et al. 1996. Role of gamma interferon in a neonatal mouse model of group B streptococcal disease. Infect. Immun. 64: 2941-2944. https://doi.org/10.1128/iai.64.8.2941-2944.1996
  27. Walsh KP, Mills KH. 2013. Dendritic cells and other innate determinants of T helper cell polarisation. Trends Immunol. 34: 521-530. https://doi.org/10.1016/j.it.2013.07.006
  28. KornT, Bettelli E, Oukka M, Kuchroo VK. 2009. IL-17 and Th17 Cells, Annu Rev. Immunol. 27: 485-517. https://doi.org/10.1146/annurev.immunol.021908.132710
  29. Bettelli E, Korn T, Kuchroo VK. 2007. Th17: the third member of the effector T cell trilogy. Curr. Opin. Immunol. 19: 652-657. https://doi.org/10.1016/j.coi.2007.07.020
  30. Yasuda K, Takeuchi Y, Hirota K. 2019. The pathogenicity of Th17 cells in autoimmune diseases. Semin. Immunopathol. 41: 283-297. https://doi.org/10.1007/s00281-019-00733-8
  31. Szulc-Dabrowska L, Gierynska M, Depczynska D, Schollenberger A, Toka FN. 2015. [Th17 lymphocytes in bacterial infections], Postepy Hig. Med. Dosw. (Online). 69: 398-417. https://doi.org/10.5604/17322693.1147868
  32. Li Y, Wei C, Xu H, Jia J, Wei X, Gou R, et al. 2018. The immunoregulation of Th17 in host against intracellular bacterial infection, Mediators Inflamm. 2018: 6587296. https://doi.org/10.1155/2018/6587296
  33. Zielinski CE, Mele F, Aschenbrenner D, Jarrossay D, Ronchi F, Gattorno M, et al. 2012. Pathogen-induced human TH17 cells produce IFN-gamma or IL-10 and are regulated by IL-1beta. Nature 484: 514-518. https://doi.org/10.1038/nature10957
  34. Ishigame H, Kakuta S, Nagai T, Kadoki M, Nam,bu A, Komiyama Y, et al. 2009. Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30: 108-119. https://doi.org/10.1016/j.immuni.2008.11.009
  35. Kagami S, Rizzo HL, Kurtz SE, Miller LS, Blauvelt A. 2010, IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense against Candida albicans. J. Immunol. 185: 5453-5462. https://doi.org/10.4049/jimmunol.1001153
  36. Ye P, Garvey PB, Zhang P, Nelson S, Bagby G, Summer WR, et al. 2001. Interleukin-17 and lung host defense against Klebsiella pneumoniae infection. Am. J. Respir. Cell Mol. Biol. 25: 335-340. https://doi.org/10.1165/ajrcmb.25.3.4424
  37. Ziegler SF, Ramsdell F, Alderson MR. 1994. The activation antigen CD69. Stem Cells 12: 456-465. https://doi.org/10.1002/stem.5530120502
  38. Wang B, Dileepan T, Briscoe S, Hyland KA, Kang J, Khoruts A, et al. 2010. Induction of TGF-beta1 and TGF-beta1-dependent predominant Th17 differentiation by group A streptococcal infection. Proc. Natl. Acad. Sci. USA. 107: 5937-5942. https://doi.org/10.1073/pnas.0904831107
  39. Yang L, Anderson DE, Baecher-Allan C, Hastings WD, Bettelli E, Oukka M, et al. 2008. IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 454: 350-352. https://doi.org/10.1038/nature07021
  40. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. 2006. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441: 235-238. https://doi.org/10.1038/nature04753
  41. Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B. 2006. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24: 179-189. https://doi.org/10.1016/j.immuni.2006.01.001
  42. McGeachy MJ, Bak-Jensen KS, Chen Y, Tato CM, Blumenschein W, McClanahan T, et al. 2007. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology. Nat. Immunol. 8: 1390-1397. https://doi.org/10.1038/ni1539
  43. Mangan PR, Harrington LE, O'Quinn DB, helms WS, Bullard DC,Elson Co, et al. 2006. Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441: 231-234. https://doi.org/10.1038/nature04754
  44. Fooksman DR. 2014. Organizing MHC Class II Presentation. Front. Immunol. 5: 158. https://doi.org/10.3389/fimmu.2014.00158
  45. Conti HR, Gaffen SL. 2015. IL-17-Mediated immunity to the opportunistic fungal pathogen Candida albicans. J. Immunol. 195: 780-788. https://doi.org/10.4049/jimmunol.1500909
  46. Yu W, Yao D, Yu S, Wang X, Li X, Wang M, et al. 2018. Protective humoral and CD4+ T cellular immune responses of Staphylococcus aureus vaccine MntC in a murine peritonitis model. Sci. Rep. 8: 3580. https://doi.org/10.1038/s41598-018-22044-y
  47. Bai H, Cheng J, Gao X, Joyee AG, Fan Y, Wang S, et al. 2009. IL-17/Th17 promotes type 1 T cell immunity against pulmonary intracellular bacterial infection through modulating dendritic cell function. J. Immunol. 183: 5886-5895. https://doi.org/10.4049/jimmunol.0901584
  48. Zhang X, Gao L, Lei L, Zhong Y, Dube P, Berton MT, et al. 2009. A MyD88-dependent early IL-17 production protects mice against airway infection with the obligate intracellular pathogen Chlamydia muridarum. J. Immunol. 183: 1291-300. https://doi.org/10.4049/jimmunol.0803075
  49. Lin JS, Kummer LW, Szaba FM, Smiley ST. 2011. IL-17 contributes to cell-mediated defense against pulmonary Yersinia pestis infection. J. Immunol. 186: 1675-1684. https://doi.org/10.4049/jimmunol.1003303
  50. Lu YJ, Gross J, Bogaert D, Finn A, Bagrase L, Zhang Q, et al. 2008. Interleukin-17A mediates acquired immunity to pneumococcal colonization, PLoS Pathog. 4: e1000159. https://doi.org/10.1371/journal.ppat.1000159
  51. Beringer A, Noack M, Miossec P. 2016. IL-17 in chronic inflammation: from discovery to targeting. Trends Mol. Med. 22: 230-241. https://doi.org/10.1016/j.molmed.2016.01.001
  52. Zelante T, De Luca A, Bonifazi P, Montagnoli C, Bozza S, Moretti S, et al. 2007. IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance. Eur. J. Immunol. 37: 2695-2706. https://doi.org/10.1002/eji.200737409
  53. Chai LY, van de Veerdonk F, Marijnissen RJ, Cheng S-C, Khoo AL, Hectors M, et al. 2010. Anti-aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity. Immunology 130: 46-54. https://doi.org/10.1111/j.1365-2567.2009.03211.x
  54. Arachchi PS, Fernando N, Weerasekera MM, Senevirathna B, Weerasekera DD, Gunasekara CP. 2017. Proinflammatory cytokine IL-17 shows a significant association with Helicobacter pylori infection and disease severity. Gastroenterol. Res. Pract. 2017: 6265150.