1887

Abstract

Lactobacilli are the dominant bacteria of the vaginal tract of healthy women and they play a major role in the maintenance of mucosal homeostasis, preventing genital infections, such as bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). It is now known that one mechanism of this protection is the influence that lactobacilli can exert on host immune responses. In this context, we evaluated two strains ( 59 and 137) for their immunomodulatory properties in response to (BV) or (VVC) infections in a HeLa cell infection model. and triggered the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) and the activation of NF-κB in HeLa cells, in contrast to 59 and 137. Treatments with the strains or their cell-free supernatants before (pre-treatment) or after (post-treatment) the challenge with the pathogens resulted in decreased secretion of pro-inflammatory cytokines and decreased activation of NF-κB. The treatments with strains not only decreased the secretion of IL-8, but also its expression, as confirmed by gene reporter luciferase assay, suggesting transcription-level control by lactobacilli. In conclusion, 59 and 137 were confirmed to have an anti-inflammatory effect against and and they were able to influence signalling in NF-κB pathway, making them interesting candidates as probiotics for the prevention or treatment of BV and VVC.

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2018-03-01
2024-03-29
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References

  1. Nunn KL, Forney LJ. Unraveling the dynamics of the human vaginal microbiome. Yale J Biol Med 2016; 89:331–337[PubMed]
    [Google Scholar]
  2. Hainer BL, Gibson MV. Vaginitis: diagnostic and treatment. Am Fam Physician 2011; 83:807–815
    [Google Scholar]
  3. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins Gynecology. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Obstet Gynecol 2006; 107:1195–1206 [Crossref]
    [Google Scholar]
  4. Ma B, Forney LJ, Ravel J. Vaginal microbiome: rethinking health and disease. Annu Rev Microbiol 2012; 66:371–389 [View Article][PubMed]
    [Google Scholar]
  5. Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev 2010; 23:253–273 [View Article][PubMed]
    [Google Scholar]
  6. Verstraelen H, Swidsinski A. The biofilm in bacterial vaginosis: implications for epidemiology, diagnosis and treatment. Curr Opin Infect Dis 2013; 26:86–89 [View Article][PubMed]
    [Google Scholar]
  7. Aldunate M, Srbinovski D, Hearps AC, Latham CF, Ramsland PA et al. 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 [View Article][PubMed]
    [Google Scholar]
  8. Fichorova RN, Cronin AO, Lien E, Anderson DJ, Ingalls RR. Response to Neisseria gonorrhoeae by cervicovaginal epithelial cells occurs in the absence of toll-like receptor 4-mediated signaling. J Immunol 2002; 168:2424–2432 [View Article][PubMed]
    [Google Scholar]
  9. Mitchell C, Marrazzo J. Bacterial vaginosis and the cervicovaginal immune response. Am J Reprod Immunol 2014; 71:555–563 [View Article][PubMed]
    [Google Scholar]
  10. Santos CM, Pires MC, Leão TL, Hernández ZP, Rodriguez ML et al. Selection of Lactobacillus strains as potential probiotics for vaginitis treatment. Microbiology 2016; 162:1195–1207 [View Article][PubMed]
    [Google Scholar]
  11. Strober W. Trypan blue exclusion test of cell viability. Curr Protoc Immunol 2015; 111:A3.B.1–A3.B.3 [Crossref]
    [Google Scholar]
  12. Abramov V, Khlebnikov V, Kosarev I, Bairamova G, Vasilenko R et al. Probiotic properties of Lactobacillus crispatus 2,029: homeostatic interaction with cervicovaginal epithelial cells and antagonistic activity to genitourinary pathogens. Probiotics Antimicrob Proteins 2014; 6:165–176 [View Article][PubMed]
    [Google Scholar]
  13. Zhao D, Keates AC, Kuhnt-Moore S, Moyer MP, Kelly CP et al. Signal transduction pathways mediating neurotensin-stimulated interleukin-8 expression in human colonocytes. J Biol Chem 2001; 276:44464–44471 [View Article][PubMed]
    [Google Scholar]
  14. Zamanian-Daryoush M, Mogensen TH, Didonato JA, Williams BR. NF-κB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-κB-inducing kinase and IκB kinase. Mol Cell Biol 2000; 20:1278–1290 [View Article][PubMed]
    [Google Scholar]
  15. Ledger WJ, Witkin SS. (editors) Bacterial vaginosis. In Vulvovaginal Infections, 2nd ed. New York, FL: CRC Press; 2016 pp. 47–55 [Crossref]
    [Google Scholar]
  16. Kyongo JK, Crucitti T, Menten J, Hardy L, Cools P et al. Cross-sectional analysis of selected genital tract immunological markers and molecular vaginal microbiota in sub-Saharan African Women, with relevance to HIV risk and prevention. Clin Vaccine Immunol 2015; 22:526–538 [View Article][PubMed]
    [Google Scholar]
  17. Aggarwal BB, Gupta SC, Kim JH. Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood 2012; 119:651–665 [View Article][PubMed]
    [Google Scholar]
  18. Barton BE, Shortall J, Jackson JV. Interleukins 6 and 11 protect mice from mortality in a staphylococcal enterotoxin-induced toxic shock model. Infect Immun 1996; 64:714–718[PubMed]
    [Google Scholar]
  19. Cauci S, Culhane JF, di Santolo M, McCollum K. Among pregnant women with bacterial vaginosis, the hydrolytic enzymes sialidase and prolidase are positively associated with interleukin-1β. Am J Obstet Gynecol 2008; 198:132.e1–132.e7 [View Article][PubMed]
    [Google Scholar]
  20. Thurman AR, Doncel GF. Innate immunity and inflammatory response to Trichomonas vaginalis and bacterial vaginosis: relationship to HIV acquisition. Am J Reprod Immunol 2011; 65:89–98 [View Article][PubMed]
    [Google Scholar]
  21. Libby EK, Pascal KE, Mordechai E, Adelson ME, Trama JP. Atopobium vaginae triggers an innate immune response in an in vitro model of bacterial vaginosis. Microbes Infect 2008; 10:439–446 [View Article][PubMed]
    [Google Scholar]
  22. Eade CR, Diaz C, Wood MP, Anastos K, Patterson BK et al. Identification and characterization of bacterial vaginosis-associated pathogens using a comprehensive cervical-vaginal epithelial coculture assay. PLoS One 2012; 7:e50106 [View Article][PubMed]
    [Google Scholar]
  23. Yano J, Noverr MC, Fidel PL. Cytokines in the host response to Candida vaginitis: Identifying a role for non-classical immune mediators, S100 alarmins. Cytokine 2012; 58:118–128 [View Article][PubMed]
    [Google Scholar]
  24. Fidel PL, Barousse M, Espinosa T, Ficarra M, Sturtevant J et al. An intravaginal live Candida challenge in humans leads to new hypotheses for the immunopathogenesis of vulvovaginal candidiasis. Infect Immun 2004; 72:2939–2946 [View Article][PubMed]
    [Google Scholar]
  25. Wagner RD, Johnson SJ. Probiotic lactobacillus and estrogen effects on vaginal epithelial gene expression responses to Candida albicans . J Biomed Sci 2012; 19:58 [View Article][PubMed]
    [Google Scholar]
  26. Rizzo A, Losacco A, Carratelli CR. Lactobacillus crispatus modulates epithelial cell defense against Candida albicans through toll-like receptors 2 and 4, interleukin 8 and human β-defensins 2 and 3. Immunol Lett 2013; 156:102–109 [View Article][PubMed]
    [Google Scholar]
  27. Petrova MI, Lievens E, Malik S, Imholz N, Lebeer S. Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Front Physiol 2015; 6:81 [View Article][PubMed]
    [Google Scholar]
  28. Hoffmann A, Levchenko A, Scott ML, Baltimore D. The IκB-NF-κB signaling module: temporal control and selective gene activation. Science 2002; 298:1241–1245 [View Article][PubMed]
    [Google Scholar]
  29. Sakai M, Ishiyama A, Tabata M, Sasaki Y, Yoneda S et al. Relationship between cervical mucus interleukin-8 concentrations and vaginal bacteria in pregnancy. Am J Reprod Immunol 2004; 52:106–112 [View Article][PubMed]
    [Google Scholar]
  30. Rose WA, McGowin CL, Spagnuolo RA, Eaves-Pyles TD, Popov VL et al. Commensal bacteria modulate innate immune responses of vaginal epithelial cell multilayer cultures. PLoS One 2012; 7:e32728 [View Article][PubMed]
    [Google Scholar]
  31. Zalenskaya IA, Joseph T, Bavarva J, Yousefieh N, Jackson SS et al. Gene expression profiling of human vaginal cells in vitro discriminates compounds with pro-inflammatory and mucosa-altering properties: novel biomarkers for preclinical testing of HIV microbicide candidates. PLoS One 2015; 10:e0128557 [View Article][PubMed]
    [Google Scholar]
  32. Ma D, Forsythe P, Bienenstock J. Live Lactobacillus reuteri is essential for the inhibitory effect on tumor necrosis factor alpha-induced interleukin-8 expression. Infect Immun 2004; 72:5308–5314 [View Article][PubMed]
    [Google Scholar]
  33. Yamamoto HS, Xu Q, Fichorova RN. Homeostatic properties of Lactobacillus jensenii engineered as a live vaginal anti-HIV microbicide. BMC Microbiol 2013; 13:4 [View Article][PubMed]
    [Google Scholar]
  34. Tak PP, Firestein GS. NF-κB: a key role in inflammatory diseases. J Clin Invest 2001; 107:7–11 [View Article][PubMed]
    [Google Scholar]
  35. Petrova MI, Lievens E, Verhoeven TL, Macklaim JM, Gloor G et al. The lectin-like protein 1 in Lactobacillus rhamnosus GR-1 mediates tissue-specific adherence to vaginal epithelium and inhibits urogenital pathogens. Sci Rep 2016; 6:3743 [View Article][PubMed]
    [Google Scholar]
  36. Malik S, Petrova MI, Imholz NC, Verhoeven TL, Noppen S et al. High mannose-specific lectin Msl mediates key interactions of the vaginal Lactobacillus plantarum isolate CMPG5300. Sci Rep 2016; 6:37339 [View Article][PubMed]
    [Google Scholar]
  37. Tachedjian G, Aldunate M, Bradshaw CS, Cone RA. The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res Microbiol 2017; 168:782–792 [View Article][PubMed]
    [Google Scholar]
  38. Mares D, Simoes JA, Novak RM, Spear GT. TLR2-mediated cell stimulation in bacterial vaginosis. J Reprod Immunol 2008; 77:91–99 [View Article][PubMed]
    [Google Scholar]
  39. Watanabe T, Nishio H, Tanigawa T, Yamagami H, Okazaki H et al. Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small intestinal injury: involvement of lactic acid. Am J Physiol Gastrointest Liver Physiol 2009; 297:G506–G513 [View Article][PubMed]
    [Google Scholar]
  40. Hearps A, Gugasyan R, Srbinovski D, Tyssen D, Aldunate M et al. Lactic acid, a vaginal microbiota metabolite, elicits an anti-inflammatory response from vaginal and cervical epithelial cells. AIDS Res Hum Retroviruses 2014; 30:A238–A239 [View Article]
    [Google Scholar]
  41. Hearps AC, Tyssen D, Srbinovski D, Bayigga L, Diaz DJD et al. Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition. Mucosal Immunol 2017; 10:1480–1490 [View Article][PubMed]
    [Google Scholar]
  42. Chon H, Choi B, Jeong G, Lee E, Lee S. Suppression of proinflammatory cytokine production by specific metabolites of Lactobacillus plantarum 10hk2 via inhibiting NF-κB and p38 MAPK expressions. Comp Immunol Microbiol Infect Dis 2010; 33:e41-49 [View Article][PubMed]
    [Google Scholar]
  43. Turner MD, Nedjai B, Hurst T, Pennington DJ. Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta 2014; 1843:2563–2582 [View Article][PubMed]
    [Google Scholar]
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