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Vaginal immunity in bacterial vaginosis

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Abstract

Vaginal immunity in response to microbial perturbation is still poorly understood and may be crucial for protection from adverse outcomes associated with bacterial vaginosis (BV). BV is the most prevalent vaginal disorder in adult women worldwide. However, its pathogenesis is still elusive. In BVpositive women, inflammatory signs are scant—approximately 50% of women are asymptomatic. The number of vaginal neutrophils in the BV-positive patient is not increased with respect to healthy women. In contrast, vaginal interleukin (IL)-1β levels are largely increased. Recent findings indicate that microbial hydrolytic enzymes could be responsible for dampening the expected proinflammatory response cascade after IL-1β increase. In other words, BV causes a large increase of vaginal IL-1β, which is not paralleled by an increase of IL-8 levels, suggesting that BV-associated factors specifically dampen IL-8. The impairment of IL-8 increase may explain the absence of neutrophil increase in most women exposed to a massive abnormal anaerobic vaginal colonization (BV). Among BV-positive women, vaginal innate immunity is strongly correlated to a specific adaptive immune response: the immunoglobulin A (IgA) against the hemolysin produced by Gardnerella vaginalis (anti-Gvh IgA), which is the main bacterium present in BV. High anti-Gvh IgA levels are protective for adverse pregnancy outcomes. However, an exaggerated inflammatory response, mainly attributed to genetic polymorphisms, is also implicated in BV-associated adverse outcomes.

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References and Recommended Reading

  1. Eschenbach DA: History and review of bacterial vaginosis. Am J Obstet Gynecol 1993, 169:441–445.

    PubMed  CAS  Google Scholar 

  2. Hillier SL, Nugent RP, Eschenbach DA, et al.: Association between bacterial vaginosis and preterm delivery of a lowbirth-weight infant. N Engl J Med 1995, 333:1737–1742.

    Article  PubMed  CAS  Google Scholar 

  3. McGregor JA, French JI: Bacterial vaginosis in pregnancy. Obstet Gynecol Surv 2000, 55:S1-S19.

    Article  PubMed  CAS  Google Scholar 

  4. Cauci S, Driussi S, De Santo D, et al.: Prevalence of bacterial vaginosis and vaginal flora changes in peri- and postmenopausal women. J Clin Microbiol 2002, 40:2147–2152.

    Article  PubMed  Google Scholar 

  5. Alvarez-Olmos MI, Barousse MM, Rajan L, et al.: Vaginal lactobacilli in adolescent presence and relationship to local and systemic immunity, and to bacterial vaginosis. Sex Transm Dis 2004, 31:393–400. This is the more recent investigation of immunity and BV in adolescent women, a female population at high risk for adverse outcomes associated with BV.

    Article  PubMed  Google Scholar 

  6. Hillier SL, Martius J, Krohn M, et al.: A case-control study of chorionamniotic infection and histologic chorioamnionitis in prematurity. N Engl J Med 1988, 319:972–978.

    Article  PubMed  CAS  Google Scholar 

  7. Goldenberg RL, Culhane JF: Infection as a cause of preterm birth. Clin Perinatol 2003, 30:677–700.

    Article  PubMed  Google Scholar 

  8. Ralph SG, Rutherford AJ, Wilson JD: Influence of bacterial vaginosis on conception and miscarriage in the first trimester: cohort study. Br Med J 1999, 319:220–223.

    CAS  Google Scholar 

  9. Sweet RL: Gynecologic conditions and bacterial vaginosis: implications for the non-pregnant patient. Infect Dis Obstet Gynecol 2000, 8:184–190.

    Article  PubMed  CAS  Google Scholar 

  10. Ness RB, Soper DE, Holley RL, et al.: Douching and endometritis: results from the PID evaluation and clinical health (PEACH) study. Sex Transm Dis 2001, 28:240–245.

    Article  PubMed  CAS  Google Scholar 

  11. Guaschino S, De Santo D, De Seta F: New perspectives in antibiotic prophylaxis for obstetric and gynaecological surgery. J Hosp Infect 2002, 50(Suppl A):S13-S16.

    Article  PubMed  Google Scholar 

  12. Sewankambo N, Gray RH, Wawer MJ, et al.: HIV-1 infection associated with abnormal vaginal flora morphology and bacterial vaginosis. Lancet 1997, 350:546–550.

    Article  PubMed  CAS  Google Scholar 

  13. Taha TE, Hoover DR, Dallabetta GA, et al.: Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 1998, 12:1699–1706.

    Article  PubMed  CAS  Google Scholar 

  14. Thorsen P, Jensen IP, Jeune B, et al.: Few microorganisms associated with bacterial vaginosis may constitute the pathologic core: a population-based microbiologic study among 3596 pregnant women. Am J Obstet Gynecol 1998, 178:580–587.

    Article  PubMed  CAS  Google Scholar 

  15. Amsel R, Totten PA, Spiegel CA, et al.: Nonspecific vaginitis: diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983, 74:14–22.

    Article  PubMed  CAS  Google Scholar 

  16. Nugent RP, Krohn MA, Hillier SL: Reliability of diagnosing bacterial vaginosis is improved by a standardized method of Gram stain interpretation. J Clin Microbiol 1991, 29:297–301.

    PubMed  CAS  Google Scholar 

  17. Sexually transmitted diseases treatment guidelines 2002. MMWR Recomm Rep 2002, 51:1–78.

  18. Wilson J: Managing recurrent bacterial vaginosis. Sex Transm Infect 2004, 80:8–11.

    Article  PubMed  CAS  Google Scholar 

  19. McDonald H, Brocklehurst P, Parson J, Vigneswaran R: Antibiotics for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev 2003, CD000262.

  20. Russell MW, Sparling FP, Morrison RP, et al.: Mucosal immunology of sexually transmitted diseases. In Mucosal Immunology, edn 3. Edited by Mestecky J, Bienenstock J, Lamm ME, et al. Oxford, UK: Elsevier; 2004, In press. This is a comprehensive and highly qualified new handbook regarding mucosal immunology.

    Google Scholar 

  21. Fidel PL: Immune regulation and its role in the pathogenesis of Candida vaginitis. Curr Infect Dis Rep 2003, 5:488–493.

    PubMed  Google Scholar 

  22. Cauci S, Monte R, Ropele M, et al.: Pore-forming and haemolytic properties of the Gardnerella vaginalis cytolysin. Mol Microbiol 1993, 9:1143–1155.

    Article  PubMed  CAS  Google Scholar 

  23. Cauci S, Monte R, Quadrifoglio F, et al.: Ionic factors regulating the interaction of Gardnerella vaginalis hemolysin with red blood cell. Biochim Biophys Acta 1993, 1153:53–58.

    Article  PubMed  CAS  Google Scholar 

  24. Cauci S, Scrimin F, Driussi S, et al.: Specific immune response against Gardnerella vaginalis hemolysin in patients with bacterial vaginosis. Am J Obstet Gynecol 1996, 175:1601–1605.

    Article  PubMed  CAS  Google Scholar 

  25. Platz-Christensen JJ, Mattsby-Baltzer I, Thomsen P, Wiqvist N: Endotoxin and interleukin-1 alpha in the cervical mucus and vaginal fluid of pregnant women with bacterial vaginosis. Am J Obstet Gynecol 1993, 169:1161–1166.

    PubMed  CAS  Google Scholar 

  26. Imseis HM, Greig PC, Livengood CH 3rd, et al.: Characterization of the inflammatory cytokines in the vagina during pregnancy and labor and with bacterial vaginosis. J Soc Gynecol Investig 1997, 4:90–94.

    Article  PubMed  CAS  Google Scholar 

  27. Sturm-Ramirez K, Gaye-Diallo A, Eisen G, et al.: High levels of tumor necrosis factor-alpha and interleukin-1beta in bacterial vaginosis may increase susceptibility to human immunodeficiency virus. J Infect Dis 2000, 182:467–473.

    Article  PubMed  CAS  Google Scholar 

  28. Cauci S, Driussi S, Guaschino S, et al.: Correlation of local interleukin-1beta levels with specific IgA response against Gardnerella vaginalis cytolysin in women with bacterial vaginosis. Am J Reprod Immunol 2002, 47:257–264. This paper first demonstrated a link between innate and adaptive vaginal immunity in BV.

    Article  PubMed  Google Scholar 

  29. Cauci S, Guaschino S, de Aloysio D, et al.: Interrelationships of interleukin-8 with interleukin-1beta and neutrophils in vaginal fluid of healthy and bacterial vaginosis positive women. Mol Hum Reprod 2003, 9:53–58. This paper reports data showing that vaginal IL-8 and IL-1β are positive correlated to vaginal neutrophils. This investigation explored the reasons for absence of inflammatory signs in BVpositive women—the strong IL-1β increase is not paralleled by the expected IL-8 increase. Factors in BV inhibit IL-8 and thus prevent mounting of neutrophil defense.

    Article  PubMed  CAS  Google Scholar 

  30. Genç MR, Witkin SS, Delaney ML, et al.: A disproportionate increase in IL-1beta over IL-1ra in the cervicovaginal secretions of pregnant women with altered vaginal microflora correlates with preterm birth. Am J Obstet Gynecol 2004, 190:1191–1197. This investigation illustrated the importance of the balance between pro- and anti-inflammatory response in women with altered vaginal flora in relation to preterm birth.

    PubMed  Google Scholar 

  31. Mattsby-Baltzer I, Platz-Christensen JJ, Hosseini N, Rosen P: IL-1beta, IL-6, TNFalpha, fetal fibronectin, and endotoxin in the lower genital tract of pregnant women with bacterial vaginosis. Acta Obstet Gynecol Scand 1998, 77:701–706.

    Article  PubMed  CAS  Google Scholar 

  32. Yudin MH, Landers DV, Meyn L, Hillier SL: Clinical and cervical cytokine response to treatment with oral or vaginal metronidazole for bacterial vaginosis during pregnancy: a randomized trial. Obstet Gynecol 2003, 102:527–534. This is the first study that investigated innate immunity before and after BV therapy.

    Article  PubMed  CAS  Google Scholar 

  33. Cauci S, Guaschino S, Driussi S, et al.: Correlation of local interleukin-8 with immunoglobulin A against Gardnerella vaginalis hemolysin and with prolidase and sialidase levels in women with bacterial vaginosis. J Infect Dis 2002, 185:1614–1620. This paper showed that microbial hydrolytic enzymes can modulate innate and adaptive immunity in vaginal mucosa of BVpositive women.

    Article  PubMed  CAS  Google Scholar 

  34. Medzhitov R, Janeway CA Jr: Innate immune induction of the adaptive immune response. Cold Spring Harb Symp Quant Biol 1999, 64:429–435.

    Article  PubMed  CAS  Google Scholar 

  35. Dinarello CA: Biologic basis for interleukin-1 in disease. Blood 1996, 87:2095–2147.

    PubMed  CAS  Google Scholar 

  36. Zara F, Nappi RE, Brerra R, et al.: Markers of local immunity in cervico-vaginal secretions of HIV infected women: implications for HIV shedding. Sex Transm Infect 2004, 80:108–112.

    Article  PubMed  CAS  Google Scholar 

  37. Ryu JS, Kang JH, Jung SY, et al.: Production of interleukin-8 by human neutrophils stimulated with Trichomonas vaginalis. Infect Immun 2004, 72:1326–1332.

    Article  PubMed  CAS  Google Scholar 

  38. Cauci S: Mucosal immune response and microbial factors in bacterial vaginosis. In Vaginal Flora in Health and Disease. Old Herborn University Seminar Monograph 12. Edited by Heidt PJ, Carter PB, Rusch VD, van der Waaij D. Herborn, Germany: Herborn Litterae; 1999:27–37. This is an overview of microbial/host interactions as markers for severity of BV.

    Google Scholar 

  39. Cauci S, Guaschino S, de Aloysio D, et al.: Correlation of innate immune response with IgA against Gardnerella vaginalis cytolysin in women with bacterial vaginosis. Ann N Y Acad Sci 2003, 987:299–301.

    Article  CAS  Google Scholar 

  40. Cauci S, Monte R, Driussi S, et al.: Impairment of the mucosal immune system: IgA and IgM cleavage detected in vaginal washings of a subgroup of patients with bacterial vaginosis. J Infect Dis 1998, 178:1698–1706. This paper demonstrated the cleavage of vaginal IgA and IgM in BV.

    Article  PubMed  CAS  Google Scholar 

  41. Cauci S, Driussi S, Ceccone S, et al.: Immunoglobulin A response against Gardnerella vaginalis hemolysin and sialidase activity in bacterial vaginosis. Am J Obstet Gynecol 1998, 178:511–515.

    Article  PubMed  CAS  Google Scholar 

  42. Romero R, Chaiworapongsa T, Kuivaniemi H, Tromp G: Bacterial vaginosis, the inflammatory response and the risk of preterm birth: a role for genetic epidemiology in the prevention of preterm birth. Am J Obstet Gynecol 2004, 190:1509–1519. This is a comprehensive overview of the state of the art in BV, with indications for future directions in the field of microbial/mucosal immunity in BV with the aim to prevent adverse pregnancy outcomes.

    Article  PubMed  Google Scholar 

  43. Koumans EH, Markowitz LE, Hogan V: Indications for therapy and treatment recommendations for bacterial vaginosis in non-pregnant and pregnant women: a synthesis of data. Clin Infect Dis 2002, 35:S152-S172.

    Article  PubMed  Google Scholar 

  44. Cauci S, Thorsen P, Culhane J: Comparison of biochemical profiles of vaginal fluid in BV-positive pregnant U.S. versus European women. Am J Obstet Gynecol 2003, 189:S167.

    Article  Google Scholar 

  45. Cauci S, Thorsen P, Schendel DE, et al.: Determination of immunoglobulin A against Gardnerella vaginalis hemolysin, sialidase, and prolidase activities in vaginal fluid: implications for adverse pregnancy outcomes. J Clin Microbiol 2003, 41:435–438. This paper demonstrated that vaginal biomarkers, including levels of anti-Gvh IgA and semiquantitative levels of sialidases or prolidases, are better indicators for increased risk of pregnancy adverse outcomes than is diagnosis of BV. High levels of vaginal anti-Gvh IgA among BV-positive women were protective for preterm birth and LBW.

    Article  PubMed  CAS  Google Scholar 

  46. Cauci S, McGregor J, Thorsen P, et al.: Combination of vaginal pH with vaginal sialidase and prolidase activities for prediction of low birth weight and preterm birth. Am J Obstet Gynecol 2004, In press. This investigation showed that microbial enzyme activities, which are known to negatively affect anti-Gvh IgA response, are predictive vaginal biomarkers for early preterm birth and very LBW.

  47. Macones GA, Parry S, Elkousy M, et al.: A polymorphism in the promoter region of TNF and bacterial vaginosis: preliminary evidence of gene-environment interaction in the etiology of spontaneous preterm birth. Am J Obstet Gynecol 2004, 190:1504–1508. This paper first described the combination of a gene polymorphism with presence of BV as a risk factor for spontaneous preterm birth.

    Article  PubMed  CAS  Google Scholar 

  48. Andrews WW: Cervicovaginal cytokines, vaginal infection, and preterm birth. Am J Obstet Gynecol 2004, 190:1179.

    Article  PubMed  Google Scholar 

  49. Donders GG, Bosmans E, Dekeermaecker A, et al.: Pathogenesis of abnormal vaginal bacterial flora. Am J Obstet Gynecol 2000, 182:872–878.

    Article  PubMed  CAS  Google Scholar 

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Cauci, S. Vaginal immunity in bacterial vaginosis. Curr Infect Dis Rep 6, 450–456 (2004). https://doi.org/10.1007/s11908-004-0064-8

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