The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Drozhdina M.B.

Kirov State Medical University

Vaginal microbiota, immune response and some sexually transmitted infections: mechanisms of interaction and regulation of the vaginal ecosystem

Authors:

Drozhdina M.B.

More about the authors

Read: 4668 times


To cite this article:

Drozhdina MB. Vaginal microbiota, immune response and some sexually transmitted infections: mechanisms of interaction and regulation of the vaginal ecosystem. Russian Journal of Clinical Dermatology and Venereology. 2020;19(6):926‑933. (In Russ.)
https://doi.org/10.17116/klinderma202019061926

Recommended articles:
Bacterial vagi­nosis: modern views. Russian Journal of Clinical Dermatology and Vene­reology. 2025;(3):261-268
Lactobacilli and bacterial vagi­nosis. Species typing and analysis of content levels in the microbiome. Mole­cular Gene­tics, Microbiology and Viro­logy. 2025;(2):43-50
Correction of vagi­nal microbiocenosis in bacterial vagi­nosis. Promising areas. Russian Bulletin of Obstetrician-Gynecologist. 2025;(4):44-50

References:

  1. Grice EA, Segre JA. The skin microbiome. Nat Rev Microbiol. 2011;9(4): 244-253. 
  2. Gevers Dirk, et al. The Human Microbiome Project: a community resource for the healthy human microbiome. PLoS Biology. 2012;10(8):e1001377.
  3. Yutinsky EM, Dvoriansky SA, Drozhdina MB. Features of the fetal state in women with fetoplacental insufficiency, depending on the therapy carried out during pregnancy. Current issues of obstetrics and gynecology, neonatology and neonatal surgery. Proceedings of the scientific and practical conference dedicated to the 100th anniversary of medical education in the Perm region. FSBEI HE VPO PGMA named after acad. E.A. Wagner Ministry of health of Russia; 2015. (In Russ.).
  4. Yutinsky EM, Dvoriansky SA, Drozhdina MB. Pregnancy and childbirth in women with fetoplacental insufficiency. Scientific Bulletin of the Belgorod state University. Series: Medicine. Pharmacy. 2014;18(189):54-57. (In Russ.).
  5. King AE, Critchley HOD, Kelly RW. Innate immune defences in the human endometrium. Reprod. Biol. Endocrinol. 2003;1:116.  https://doi.org/10.1186/1477-7827-1-116
  6. King AE, Wheelhouse N, Cameron S, McDonald SE, Lee K-F, Entrican G, Critchley HO, Horne AW. Expression of secretory leukocyte protease inhibitor and elafin in human fallopian tube and in an in-vitro model of Chlamydia trachomatis infection. Hum Reprod. 2009;24:679-686.  https://doi.org/10.1093/humrep/den452
  7. Chen A, McKinley SA, Wang S, Shi F, Mucha PJ, Forest MG, Lai SK. Transient antibody-mucin interactions produce a dynamic molecular shield against viral invasion. Biophys J. 2014;106:2028-2036. https://doi.org/10.1016/j.bpj.2014.02.038
  8. Ghadimi D, de Vrese M, Heller KJ, Schrezenmeir J. Lactic acid bacteria enhance autophagic ability of mononuclear phagocytes by increasing Th1 autophagy-promoting cytokine (IFN-gamma) and nitric oxide (NO) levels and reducing Th2 autophagy-restraining cytokines (IL-4 and IL-13) in response to Mycobacteriu. Int. Immunopharmacol. 2010;10:694-706.  https://doi.org/10.1016/j.intimp.2010.03.014
  9. Aldunate M, Srbinovski D, Hearps AC, Latham CF, Ramsland PA, Gugasyan R, Cone RA, Tachedjian G. Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis. Front. Physiol. 2015;6:164.  https://doi.org/10.3389/fphys.2015.00164
  10. Gajer P, Brotman RM, Bai G, Sakamoto J, Schutte UME, Zhong X, Koenig SS, Fu L, Ma ZS, Zhou X, et al. Temporal dynamics of the human vaginal microbiota. Sci Transl Med. 2012;4:132ra52. https://doi.org/10.1126/scitranslmed.3003605
  11. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SSK, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA. 2011;108:4680-4687. https://doi.org/10.1073/pnas.1002611107
  12. Anahtar MN, Byrne EH, Doherty KE, Bowman BA, Yamamoto HS, Soumillon M, Padavattan N, Ismail N, Moodley A, Sabatini ME, et al. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract. Immunity. 2015;42:965-976.  https://doi.org/10.1016/j.immuni.2015.04.019
  13. Muzny CA, Schwebke JR. Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses. J Infect Dis. 2016;214:1-5.  https://doi.org/10.1093/infdis/jiw121
  14. Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, Viscidi RP, Burke AE, Ravel J, Gravitt PE. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause. 2014;21:450-458.  https://doi.org/10.1097/GME.0b013e3182a4690b
  15. Lee SK, Kim CJ, Kim D-J, Kang J-H. Immune cells in the female reproductive tract. Immune Netw. 2015;15:16-26.  https://doi.org/10.4110/in.2015.15.1.16
  16. Aflatoonian R, Fazeli A. Toll-like receptors in female reproductive tract and their menstrual cycle dependent expression. J Reprod Immunol. 2008;77:7-13.  https://doi.org/10.1016/j.jri.2007.03.014
  17. Hart KM, Murphy AJ, Barrett KT, Wira CR, Guyre PM, Pioli PA. Functional expression of pattern recognition receptors in tissues of the human female reproductive tract. J Reprod Immunol. 2009;80:33-40.  https://doi.org/10.1016/j.jri.2008.12.004
  18. Yeaman GR, Collins JE, Fanger MW, Wira CR, Lydyard PM. CD8+ T cells in human uterine endometrial lymphoid aggregates: Evidence for accumulation of cells by trafficking. Immunology. 2001;102:434-440.  https://doi.org/10.1046/j.1365-2567.2001.01199.x
  19. Wira CR, Fahey JV, Rodriguez-Garcia M, Shen Z, Patel MV. Regulation of mucosal immunity in the female reproductive tract: the role of sex hormones in immune protection against sexually transmitted pathogens. Am J Reprod Immunol. 2014;72(2):236-258.  https://doi.org/10.1111/aji.12252
  20. Olmsted SS, Meyn LA, Rohan LC, Hillier SL. Glycosidase and proteinase activity of anaerobic gram-negative bacteria isolated from women with bacterial vaginosis. Sex Transm Dis. 2003;30:257-261.  https://doi.org/10.1097/00007435-200303000-00016
  21. Moncla BJ, Chappell CA, Mahal LK, Debo BM, Meyn LA, Hillier SL. Impact of bacterial vaginosis, as assessed by nugent criteria and hormonal status on glycosidases and lectin binding in cervicovaginal lavage samples. PLoS ONE. 2015;10:e0127091. https://doi.org/10.1371/journal.pone.0127091
  22. Nunn KL, Wang Y-Y, Harit D, Humphrys MS, Ma B, Cone R, Ravel J, Lai SK. Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota. MBio. 2015; 6(5):e01084-15.  https://doi.org/10.1128/mBio.01084-15
  23. Di Paola M, Sani C, Clemente AM, Iossa A, Perissi E, Castronovo G, Tanturli M, Rivero D, Cozzolino F, Cavalieri D, et al. Characterization of cervico-vaginal microbiota in women developing persistent high-risk Human Papillomavirus infection. Sci Rep. 2017;7:10200. https://doi.org/10.1038/s41598-017-09842-6
  24. Schellenberg JJ, Links MG, Hill JE, Dumonceaux TJ, Kimani J, Jaoko W, Wachihi C, Mungai JN, Peters GA, Tyler S, et al. Molecular definition of vaginal microbiota in East African commercial sex workers. Appl Environ Microbiol. 2011;77:4066-4074. https://doi.org/10.1128/AEM.02943-10
  25. Martin Harold LJ, Richardson BA, Nyange PM, Lavreys L, Hillier SL, Chohan B, Mandaliya K, Ndinya-Achola JO, Bwayo J, Kreiss J. Vaginal Lactobacilli, Microbial Flora, and Risk of Human Immunodeficiency Virus Type 1 and Sexually Transmitted Disease Acquisition. J Infect Dis. 1999;180:1863-1868. https://doi.org/10.1086/315127
  26. Atashili J, Poole C, Ndumbe PM, Adimora AA, Smith JS. Bacterial vaginosis and HIV acquisition: A meta-analysis of published studies. AIDS. 2008; 22:1493-1501. https://doi.org/10.1097/QAD.0b013e3283021a37
  27. Gosmann C, Anahtar MN, Handley SA, Farcasanu M, Abu-Ali G, Bowman BA, Padavattan N, Desai C, Droit L, Moodley A, et al. Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women. Immunity. 2017; 46:29-37.  https://doi.org/10.1016/j.immuni.2016.12.013
  28. McClelland RS, Lingappa JR, Srinivasan S, Kinuthia J, John-Stewart GC, Jaoko W, Richardson BA, Yuhas K, Fiedler TL, Mandaliya KN, et al. Evaluation of the association between the concentrations of key vaginal bacteria and the increased risk of HIV acquisition in African women from five cohorts: A nested case-control study. Lancet Infect Dis. 2018;18:554-564.  https://doi.org/10.1016/S1473-3099(18)30058-6
  29. Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, Allen C, Hansen G, Woodbrook R, Wolfe C, et al. The Global Burden of Cancer 2013. JAMA Oncol. 2015;1:505-527.  https://doi.org/10.1001/jamaoncol.2015.0735
  30. Doorbar J. Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci. 2006;110:525-541.  https://doi.org/10.1042/CS20050369
  31. Zur Hausen H. Papillomaviruses and cancer: From basic studies to clinical application. Nat Rev Cancer. 2002;2:342-350.  https://doi.org/10.1038/nrc798
  32. De Marco F. Oxidative stress and HPV carcinogenesis. Viruses. 2013;5:708-731.  https://doi.org/10.3390/v5020708
  33. Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, Stanley MA. The biology and life-cycle of human papillomaviruses. Vaccine. 2012;30:55-70.  https://doi.org/10.1016/j.vaccine.2012.06.083
  34. Mitra A, MacIntyre DA, Marchesi JR, Lee YS, Bennett PR, Kyrgiou M. The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: What do we know and where are we going next? Microbiome. 2016;4:58.  https://doi.org/10.1186/s40168-016-0203-0
  35. Stanley MA. Epithelial cell responses to infection with human papillomavirus. Clin Microbiol Rev. 2012;25:215-222.  https://doi.org/10.1128/CMR.05028-11
  36. Yarbrough VL, Winkle S, Herbst-Kralovetz MM. Antimicrobial peptides in the female reproductive tract: A critical component of the mucosal immune barrier with physiological and clinical implications. Hum Reprod. 2015; 21:353-377.  https://doi.org/10.1093/humupd/dmu065
  37. Karim R, Meyers C, Backendorf C, Ludigs K, Offringa R, van Ommen G-JB, Melief CJ, van der Burg SH, Boer JM. Human papillomavirus deregulates the response of a cellular network comprising of chemotactic and proinflammatory genes. PLoS ONE. 2011;6:e17848. https://doi.org/10.1371/journal.pone.0017848
  38. Sperling T, Oldak M, Walch-Ruckheim B, Wickenhauser C, Doorbar J, Pfister H, Malejczyk M, Majewski S, Keates AC, Smola S. Human papillomavirus type 8 interferes with a novel C/EBPbeta-mediated mechanism of keratinocyte CCL20 chemokine expression and Langerhans cell migration. PLoS Pathog. 2012;8:e1002833. https://doi.org/10.1371/journal.ppat.1002833
  39. Hong S, Laimins LA. The JAK-STAT transcriptional regulator, STAT-5, activates the ATM DNA damage pathway to induce HPV 31 genome amplification upon epithelial differentiation. PLoS Pathog. 2013;9:e1003295. https://doi.org/10.1371/journal.ppat.1003295
  40. Laniewski P, Barnes D, Goulder A, Cui H, Roe DJ, Chase DM, Herbst-Kralovetz MM. Linking cervicovaginal immune signatures, HPV and microbiota composition in cervical carcinogenesis in non-Hispanic and Hispanic women. Sci Rep. 2018;8:7593. https://doi.org/10.1038/s41598-018-25879-7
  41. Shannon B, Yi TJ, Perusini S, Gajer P, Ma B, Humphrys MS, Thomas-Pavanel J, Chieza L, Janakiram P, Saunders M, et al. Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota. Mucosal Immunol. 2017;10:1310-1319. https://doi.org/10.1038/mi.2016.129
  42. Bordignon V, Di Domenico EG, Trento E, D’Agosto G, Cavallo I, Pontone M, Pimpinelli F, Mariani L, Ensoli F. How Human Papillomavirus Replication and Immune Evasion Strategies Take Advantage of the Host DNA Damage Repair Machinery. Viruses. 2017;9:390.  https://doi.org/10.3390/v9120390
  43. Bonin CM, Padovani CTJ, da Costa IP, Avila LS, Ferreira AMT, Fernandes CES, dos Santos AR, Tozetti IA. Detection of regulatory T cell phenotypic markers and cytokines in patients with human papillomavirus infection. J Med Virol. 2019;91:317.  https://doi.org/10.1002/jmv.25312
  44. Smith JS, Munoz N, Herrero R, Eluf-Neto J, Ngelangel C, Franceschi S, Bosch FX, Walboomers JM, Peeling RW. Evidence for Chlamydia trachomatis as a human papillomavirus cofactor in the etiology of invasive cervical cancer in Brazil and the Philippines. J Infect Dis. 2002;185:324-331.  https://doi.org/10.1086/338569
  45. Alberts CJ, Schim van der Loeff MF, Papenfuss MR, da Silva RJC, Villa LL, Lazcano-Ponce E, Nyitray AG, Giuliano AR. Association of Chlamydia trachomatis infection and herpes simplex virus type 2 serostatus with genital human papillomavirus infection in men: The HPV in men study. Sex Transm Dis. 2013;40:508-515.  https://doi.org/10.1097/OLQ.0b013e318289c186
  46. Gao W, Weng J, Gao Y, Chen X. Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection: A cross-sectional study. BMC Infect Dis. 2013;13:271.  https://doi.org/10.1186/1471-2334-13-271
  47. Audirac-Chalifour A, Torres-Poveda K, Bahena-Roman M, Tellez-Sosa J, Martinez-Barnetche J, Cortina-Ceballos B, López-Estrada G, Delgado-Romero K, Burguete-García AI, Cantú D, et al. Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study. PLoS ONE. 2016;11:e0153274. https://doi.org/10.1371/journal.pone.0153274
  48. Gillet E, Meys JF, Verstraelen H, Bosire C, De Sutter P, Temmerman M, Broeck DV. Bacterial vaginosis is associated with uterine cervical human papillomavirus infection: A meta-analysis. BMC Infect Dis. 2011;11:10.  https://doi.org/10.1186/1471-2334-11-10
  49. Woodman CBJ, Collins SI, Young LS. The natural history of cervical HPV infection: Unresolved issues. Nat Rev Cancer. 2007;7:11-22.  https://doi.org/10.1038/nrc2050
  50. Drago F, Herzum A, Ciccarese G, Dezzana M, Casazza S, Pastorino A, Bandelloni R, Parodi A. Ureaplasma parvum as a possible enhancer agent of HPV-induced cervical intraepithelial neoplasia: Preliminary results. J Med Virol. 2016;88:2023-2024. https://doi.org/10.1002/jmv.24583
  51. Mitra A, MacIntyre DA, Lee YS, Smith A, Marchesi JR, Lehne B, Bhatia R, Lyons D, Paraskevaidis E, Li JV, et al. Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Sci Rep. 2015;5:16865. https://doi.org/10.1038/srep16865
  52. Oh HY, Kim B-S, Seo S-S, Kong J-S, Lee J-K, Park S-Y, Hong KM, Kim HK, Kim MK. The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea. Clin Microbiol Infect. 2015;21:674.e1-674.e9.  https://doi.org/10.1016/j.cmi.2015.02.026
  53. Piyathilake CJ, Ollberding NJ, Kumar R, Macaluso M, Alvarez RD, Morrow CD. Cervical Microbiota Associated with Higher Grade Cervical Intraepithelial Neoplasia in Women Infected with High-Risk Human Papillomaviruses. Cancer Prev Res. 2016;9:357-366.  https://doi.org/10.1158/1940-6207.CAPR-15-0350
  54. Mhatre M, McAndrew T, Carpenter C, Burk RD, Einstein MH, Herold BC. Cervical intraepithelial neoplasia is associated with genital tract mucosal inflammation. Sex Transm Dis. 2012;39:591-597.  https://doi.org/10.1097/OLQ.0b013e318255aeef
  55. Evans BA, Kell PD, Bond RA, MacRae KD, Slomka MJ, Brown DWG. Predictors of seropositivity to herpes simplex virus type 2 in women. Int J STD AIDS. 2003;14:30-36.  https://doi.org/10.1258/095646203321043237
  56. Sergeeva IG, Makarova NG. Modern topical therapy of patients with recurrent herpes simplex. Bulletin of Novosibirsk state University. Series: Biology, clinical medicine. 2014;1(12):94-101. (In Russ.).
  57. Masese L, Baeten JM, Richardson BA, Bukusi E, John-Stewart G, Jaoko W, McClelland RS. Incident herpes simplex virus type 2 infection increases the risk of subsequent episodes of bacterial vaginosis. J Infect Dis. 2014; 209:1023-1027. https://doi.org/10.1093/infdis/jit634
  58. Van de Perre P, Segondy M, Foulongne V, Ouedraogo A, Konate I, Huraux J-M, Mayaud P, Nagot N. Herpes simplex virus and HIV-1: Deciphering viral synergy. Lancet Infect Dis. 2008;8:490-497.  https://doi.org/10.1016/S1473-3099(08)70181-6
  59. Piot P, Van Dyck E, Totten PA, Holmes KK. Identification of Gardnerella (Haemophilus) vaginalis. J Clin Microbiol. 1982;15:19-24. 
  60. Cherpes TL, Hillier SL, Meyn LA, Busch JL, Krohn MA. A delicate balance: Risk factors for acquisition of bacterial vaginosis include sexual activity, absence of hydrogen peroxide-producing lactobacilli, black race, and positive herpes simplex virus type 2 serology. Sex Transm Dis. 2008;35:78-83.  https://doi.org/10.1097/OLQ.0b013e318156a5d0
  61. Shannon B, Gajer P, Yi TJ, Ma B, Humphrys MS, Thomas-Pavanel J, Chieza L, Janakiram P, Saunders M, Tharao W, et al. Distinct Effects of the Cervicovaginal Microbiota and Herpes Simplex Type 2 Infection on Female Genital Tract Immunology. J Infect Dis. 2017;215:1366-1375. https://doi.org/10.1093/infdis/jix088
  62. Oh JE, Kim B-C, Chang D-H, Kwon M, Lee SY, Kang D, Kim JY, Hwang I, Yu JW, Nakae S, et al. Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa. Proc Natl Acad Sci USA. 2016; 113:762-771.  https://doi.org/10.1073/pnas.1518589113
  63. Ebbo M, Crinier A, Vely F, Vivier E. Innate lymphoid cells: Major players in inflammatory diseases. Nat Rev Immunol. 2017;17:665-678.  https://doi.org/10.1038/nri.2017.86
  64. Bradshaw CS, Brotman RM. Making inroads into improving treatment of bacterial vaginosis — Striving for long-term cure. BMC Infect Dis. 2015; 15:292.  https://doi.org/10.1186/s12879-015-1027-4
  65. Anukam KC, Osazuwa E, Osemene GI, Ehigiagbe F, Bruce AW, Reid G. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Microbes Infect. 2006;8:2772-2776. https://doi.org/10.1016/j.micinf.2006.08.008

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.