Skip to main content

Advertisement

Log in

The Mechanism of IL-17 Regulating Neutrophils Participating in Host Immunity of RVVC Mice

  • General Gynecology: Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are the most common lower genital tract infections in reproductive women. In recent years, the research on its pathogenesis mainly focuses on vaginal local immunity and IL-17 as key factors in adaptive immunity, attracting much attention. However, the role of IL-17 in local immunity in VVC and RVVC is poorly understood. At the same time, neutrophils are considered the most effective way to control and eliminate candidal infection and have a controversial role in VVC and RVVC. In this study, we built a mouse RVVC model. After analyzing the vaginal lavage solution of RVVC mice with an inflammatory factor antibody chip and ELISA, we found that IL-17 may play a protective role in RVVC. The experiment of constructing RVVC mice with different concentrations of IL-17 using halofuginone and comparing the vaginal fungi load and vaginal epithelial damage verified that IL-17 had a protective effect in RVVC. In addition, in vitro and in vivo studies found that IL-17 can promote neutrophil apoptosis and recruit neutrophils in the vagina. The neutrophils in the vagina can secrete IL-17 in an autocrine manner. These two may be why IL-17 plays a protective role in RVVC. In summary, the study suggests that IL-17-mediated regulation of neutrophil function is involved in host immune response to RVVC, which helps us to further understand the potential mechanism of IL-17 in RVVC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data Availability

The authors declare that all data and materials used in this research are available for consultation.

References

  1. Rodriguez-Cerdeira C, Gregorio MC, Molares-Vila A, Lopez-Barcenas A, Fabbrocini G, Bardhi B, et al. Biofilms and vulvovaginal candidiasis. Colloids Surf B Biointerfaces. 2019;174:110–25.

    Article  CAS  PubMed  Google Scholar 

  2. Yano J, Peters BM, Noverr MC, Fidel PL Jr. Novel mechanism behind the immunopathogenesis of vulvovaginal candidiasis: “neutrophil anergy.” Infect Immun. 2018;86(3):e00684-17. https://doi.org/10.1128/IAI.00684-17.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ardizzoni A, Wheeler RT, Pericolini E. It Takes Two to Tango: How a Dysregulation of the Innate Immunity, Coupled With Candida Virulence, Triggers VVC Onset. Front Microbiol. 2021;12:692491.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kalia N, Singh J, Sharma S, Kaur M. SNPs in 3'-UTR region of MBL2 increases susceptibility to recurrent vulvovaginal infections by altering sMBL levels. Immunobiology. 2019;224(1):42–9.

    Article  CAS  PubMed  Google Scholar 

  5. Shao MK, Qi WJ, Hou MY, Luo DD. Analysis of pathogenic factors of Candida albicans and the effect of vaginal immunization on recurrent vulvovaginal candidiasis in mice. J Obstet Gynaecol Res. 2022;48(3):857–65.

    Article  CAS  PubMed  Google Scholar 

  6. Gabrielli E, Sabbatini S, Roselletti E, Kasper L, Perito S, Hube B, et al. In vivo induction of neutrophil chemotaxis by secretory aspartyl proteinases of Candida albicans. Virulence. 2016;7(7):819–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pericolini E, Gabrielli E, Amacker M, Kasper L, Cassone A. Secretory Aspartyl Proteinases Cause Vaginitis and Can Mediate Vaginitis Caused by Candida albicans in Mice. mBio. 2015;6(3):e00724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rosati D, Bruno M, Jaeger M, Ten Oever J. Recurrent vulvovaginal candidiasis: an immunological perspective. Microorganisms. 2020;8(2):144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Patel DD, Kuchroo VK. Th17 cell pathway in human immunity: lessons from genetics and therapeutic interventions. Immunity. 2015;43(6):1040–51.

    Article  CAS  PubMed  Google Scholar 

  10. Jiang L, Fang M, Tao R, Yong X, Wu T. Recombinant human interleukin 17A enhances the anti-Candida effect of human oral mucosal epithelial cells by inhibiting Candida albicans growth and inducing antimicrobial peptides secretion. J Oral Pathol Med. 2020;49(4):320–7.

    Article  CAS  PubMed  Google Scholar 

  11. Peters BM, Coleman BM, HME W, Barker KS, FEY A, Cipolla E, et al. The interleukin (IL) 17R/IL-22R signaling axis is dispensable for vulvovaginal candidiasis regardless of estrogen status. J Infect Dis. 2020;221(9):1554–63.

    Article  CAS  PubMed  Google Scholar 

  12. Pietrella D, Rachini A, Pines M, Pandey N, Mosci P, Bistoni F, et al. Th17 cells and IL-17 in protective immunity to vaginal candidiasis. PLoS One. 2011;6(7):e22770.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Klaile E, Prada Salcedo JP, Klassert TE, Besemer M, Bothe AK, Durotin A, et al. Antibody ligation of CEACAM1, CEACAM3, and CEACAM6, differentially enhance the cytokine release of human neutrophils in responses to Candida albicans. Cell Immunol. 2021;371:104459.

    Article  PubMed  Google Scholar 

  14. Luo S, Skerka C, Kurzai O, Zipfel PF. Complement and innate immune evasion strategies of the human pathogenic fungus Candida albicans. Mol Immunol. 2013;56(3):161–9.

    Article  CAS  PubMed  Google Scholar 

  15. Kobayashi SD, Voyich JM, Buhl CL. Global changes in gene expression by human polymorphonuclear leukocytes during receptor-mediated phagocytosis: Cell fate is regulated at the level of gene expression. Proc Natl Acad Sci U S A. 2002;99(10):6901–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Maimon N, Zamir ZZ, Kalkar P, Zeytuni-Timor O, Ariel A. The pro-apoptotic ARTS protein induces neutrophil apoptosis, efferocytosis, and macrophage reprogramming to promote resolution of inflammation. Apoptosis. 2020;25(7-8):558–73.

    Article  CAS  PubMed  Google Scholar 

  17. El-Houssaini HH, Elnabawy OM, Nasser HA, Elkhatib WF. Correlation between antifungal resistance and virulence factors in Candida albicans recovered from vaginal specimens. Microb Pathog. 2019;128:13–9.

    Article  CAS  PubMed  Google Scholar 

  18. Pines M, Spector I. Halofuginone - the multifaceted molecule. Molecules. 2015;20(1):573–94.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Khader SA, Gaffen SL, Kolls JK. Th17 cells at the crossroads of innate and adaptive immunity against infectious diseases at the mucosa. Mucosal Immunol. 2009;2(5):403–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015;33(1):257–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Cassone A, Vecchiarelli A, Hube B. Aspartyl proteinases of eukaryotic microbial pathogens: from eating to heating. PLoS Pathog. 2016;12(12):e1005992.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Miossec P, Kolls JK. Targeting IL-17 and TH17 cells in chronic inflammation. Nat Rev Drug Discov. 2012;11(10):763–76.

    Article  CAS  PubMed  Google Scholar 

  23. Bunte K, Beikler T. Th17 cells and the IL-23/IL-17 axis in the pathogenesis of periodontitis and immune-mediated inflammatory diseases. Int J Mol Sci. 2019;20(14):3394.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chang SH. T helper 17 (Th17) cells and interleukin-17 (IL-17) in cancer. Arch Pharm Res. 2019;42(7):549–59.

    Article  CAS  PubMed  Google Scholar 

  25. Gaffen SL. Recent advances in the IL-17 cytokine family. Curr Opin Immunol. 2011;23(5):613–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Taylor PR, Roy S, Leal SM Jr, Sun Y, Howell SJ, Cobb BA, et al. Activation of neutrophils by autocrine IL-17A-IL-17RC interactions during fungal infection is regulated by IL-6, IL-23, RORgammat and dectin-2. Nat Immunol. 2014;15(2):143–51.

    Article  CAS  PubMed  Google Scholar 

  27. Kalimo H, Zoppo G, Paetau A. Polymorphonuclear neutrophil infiltration into ischemic infarctions: myth or truth? Acta Neuropathol. 2013;125(3):313–6.

    Article  PubMed  Google Scholar 

  28. Wang W, Zhou A, Zhang X, Xiang Y, Huang Y, Wang L, et al. Interleukin 17A promotes pneumococcal clearance by recruiting neutrophils and inducing apoptosis through a p38 mitogen-activated protein kinase-dependent mechanism in acute otitis media. Infect Immun. 2014;82(6):2368–77.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sun C, Hideki F, Kono H, et al. Interleukin 17A plays a role in lipopolysaccharide/D-galactosamine-induced fulminant hepatic injury in mice. J Surg Res. 2015;199(2):487–93.

    Article  PubMed  Google Scholar 

  30. Fidel PL, Barousse M, Espinosa T, Ficarra M, Dunlap K. An intravaginal live Candida challenge in humans leads to new hypotheses for the immunopathogenesis of vulvovaginal candidiasis. Infect Immun. 2004;72(5):2939.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Cassone A, Sobel JD. Experimental models of vaginal candidiasis and their relevance to human candidiasis. Infect Immun. 2016;84(5):1255–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Petrova MI, Elke L, Shweta M, Nicole I, Sarah L. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Front Physiol. 2015;6:81.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Code Availability

Not applicable

Funding

This research was supported by a grant from the National Natural Science Foundation of China (Grant No.82260302; Grant No. 81660248) and the Yunnan Provincial Department of Education Scientific Research Fund (Grant No.2022J0259).

Author information

Authors and Affiliations

Authors

Contributions

S-MK, Q-WJ, H-MY, and L-SN conducted the experiments. Q-WJ planned and supervised the experiments. S-MK wrote the paper. All authors gave intellectual input to the study and approved the final version of the manuscript.

Corresponding author

Correspondence to Wenjin Qi.

Ethics declarations

Ethics Approval

The experiment was approved by the Institutional Animal Care and Use Committee (IACUC) at Kunming Medical University (No.kmmu2020178).

Consent to Participate

Not applicable

Consent for Publication

Not applicable

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shao, M., Hou, M., Li, S. et al. The Mechanism of IL-17 Regulating Neutrophils Participating in Host Immunity of RVVC Mice. Reprod. Sci. 30, 3610–3622 (2023). https://doi.org/10.1007/s43032-023-01291-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s43032-023-01291-z

Keywords

Navigation