Genital inflammation, immune activation and risk of sexual HIV acquisition

Current Opinion in HIV and AIDS

Volumn 11, Issue 2, 2016, Pages 156-162

  Passmore, Jo Ann S ^a,b,d   Jaspan, Heather B ^a,c   Masson, Lindi ^a,b  

^a UNIVERSITY OF CAPE TOWN   (South Africa)

^b UNIVERSITY OF KWAZULU NATAL   (South Africa)

^c SEATTLE CHILDREN S HOSPITAL   (United States)

^d NATIONAL HEALTH LABORATORY SERVICE   (South Africa)

Author keywords

cytokines; genital tract; HIV risk; inflammation; T cell activation

Indexed keywords

CHEMOKINE RECEPTOR CCR5; GAMMA INTERFERON INDUCIBLE PROTEIN 10; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; CYTOKINE;

CYTOKINE PRODUCTION; DENDRITIC CELL; FEMALE GENITAL TRACT INFLAMMATION; HEALTH CARE QUALITY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; INCIDENCE; MACROPHAGE; NONHUMAN; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SEROCONVERSION; SEXUALLY TRANSMITTED DISEASE; SIMIAN IMMUNODEFICIENCY VIRUS; SOUTH AFRICAN; TARGET CELL; VAGINITIS; AFRICA SOUTH OF THE SAHARA; FEMALE; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOLOGY; INFLAMMATION; LYMPHOCYTE ACTIVATION; MICROBIOLOGY; T LYMPHOCYTE; TRANSMISSION; VAGINA; VIROLOGY;

AFRICA SOUTH OF THE SAHARA; CYTOKINES; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; INFLAMMATION; LYMPHOCYTE ACTIVATION; T-LYMPHOCYTES; VAGINA;

EID: 84957432102     PISSN: 1746630X     EISSN: 17466318     Source Type: Journal    
DOI: 10.1097/COH.0000000000000232     Document Type: Review

References (96)

1. UNAIDS. UNAIDS Report on the global AIDS Epidemic 2010. http://www.unaids. org/globalreport/. [Accessed 15 October 2015]
2. UNAIDS. The gap report. http://www.unaids.org/en/media/unaids/contentassets/documents/unaidspublication/2014/UNAIDS-Gap-report-en.pdf. [Accessed 15 October 2015]
3. South African Department of Health Report. The 2012 National antenatal sentinel HIV & Herpes simplex type-2 prevalence survey in South Africa. (Department of Health, Pretoria, 2014). http://www.health-e.org.za/wpcontent/uploads/2014/05/ASHIVHerp-Report2014-22May2014.pdf. [Accessed 15 October 2015]
4. Kaul R, Ball TB, Hirbod T. Defining the genital immune correlates of protection against HIV acquisition: co-infections and other potential confounders. Sex Transm Infect 2011; 87: 125e130.
5. Laga M, Manoka A, Kivuvu M, et al. Nonulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. AIDS 1993; 7: 95-102.
6. 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.
7. Low N, Chersich MF, Schmidlin K, et al. Intravaginal practices, bacterial vaginosis, and HIV infection in women: individual participant data metaanalysis. PLoS Med 2011; 8: e1000416.
8. Mlisana K, Naicker N, Werner L, et al. Vaginal discharge is a poor predictor of sexually transmitted infections and subclinical genital tract inflammation in women at high-risk of HIV infection. J Infect Dis 2012; 206: 6-14.
9. Masson L, Passmore JAS, Liebenberg LJ, et al. Genital inflammation and the risk of HIV acquisition in women. Clin Infect Dis 2015; 61: 260-269.
10. Anahtar MN, Byrne EH, Doherty KE, et al. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract. Immunity 2015; 42: 965-976.
11. Li Q, Estes JD, Schlievert PM, et al. Glycerol monolaurate prevents mucosal SIV transmission. Nature 2009; 458: 1034-1038.
12. Stanford MM, Issekutz TB. The relative activity of CXCR3 and CCR5 ligands in T lymphocyte migration: concordant and disparate activities in vitro and in vivo. J Leukoc Biol 2003; 74: 791-799.
13. Wira CR, Fahey JV, Sentman CL, et al. Innate and adaptive immunity in female genital tract: cellular responses and interactions. Immunol Rev 2005; 206: 306-335.
14. Dieu-Nosjean MC, Vicari A, Lebecque S, et al. Regulation of dendritic cell trafficking: a process that involves the participation of selective chemokines. J Leukoc Biol 1999; 66: 252-262.
15. Mueller A, Strange PG. The chemokine receptor, CCR5. Int J Biochem Cell Biol 2004; 36: 35-38.
16. Nkwanyana NN, Gumbi P, Roberts L, et al. Impact of human immunodeficiency virus 1 infection and inflammation on the composition and yield of cervical mononuclear cells in the female genital tract. Immunol 2009; 128: e746-e757.
17. Arnold KB, Burgener A, Birse K, et al. Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol 2015; ePub ahead of print DOI: 10.1038/mi.2015.51.
18. Haase AT. Early events in sexual transmission of HIV and SIV and opportunities for interventions. Annu Rev Med 2011; 62: 127-139.
19. Cocchi F, DeVico AL, Garzino-Demo A, et al. Identification of RANTES, MIP- 1α, and MIP-1b as the major HIV-suppressive factors produced by CD8+ T cells. Science 1995; 270: 1811-1815.
20. Hirbod T, Nilsson J, Andersson S, et al. Upregulation of interferon-α and RANTES in the Cervix of HIV-1-seronegative women with high-risk behavior. JAIDS 2006; 43: 137-143.
21. Lajoie J, Juno J, Burgener A, et al. A distinct cytokine and chemokine profile at the genital mucosa is associated with HIV-1 protection among HIV-exposed seronegative commercial sex workers. Mucosal Immunol 2012; 5: 277-287.
22. Lajoie J, Kimani M, Plummer FA, et al. Association of sex work with reduced activation of the mucosal immune system. J Infect Dis 2014; 210: 319-329.
23. Osborn L, Kunkel S, Nabel GJ. Tumor necrosis factor-alpha and interleukin-1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A 1989; 86: 2336-3240.
24. Nazli A, Chan O, Dobson-Belaire WN, et al. Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Path 2010; 6: e1000852.
25. Naranbhai V, Karim SSA, Altfeld M, et al. Innate immune activation enhances HIV acquisition in women, diminishing the effectiveness of tenofovir microbicide gel. J Infect Dis 2012; 206: 993-1001.
26. Kahle EM, Bolton M, Hughes JP, et al. Plasma cytokine levels and risk of HIV type 1 (HIV-1) transmission and acquisition: a nested case-control study among HIV-1-serodiscordant couples. J Infect Dis 2015; 211: 1451-1460.
27. Masson L, Mlisana K, Little F, et al. Defining genital tract cytokine signatures of sexually transmitted infections and bacterial vaginosis in women at high risk of HIV infection: a cross-sectional study. Sex Transm Infect 2014; 90: 580-587.
28. Koning FA, Otto SA, Hazenberg MD, et al. Low-level CD4+ T cell activation is associated with low susceptibility to HIV-1 infection. J Immunol 2005; 175: 6117-6122.
29. Paiardini M, Cervasi B, Reyes-Aviles E, et al. Low levels of SIV infection in sooty mangabey central memory CD4+ T cells are associated with limited CCR5 expression. Nature Med 2011; 17: 830-836.
30. Jaspan HB, Liebenberg LJ, Hanekom W, et al. Immune activation in the female genital tract during HIV infection predicts mucosal CD4 depletion and HIV shedding. J Infect Dis 2011; 204: 1550-1556.
31. Levine WC, Pope V, Bhoomkar A, et al. Increase in endocervical CD4 lymphocytes among women with nonulcerative sexually transmitted diseases. J Infect Dis 1998; 177: 167-174.
32. Fichorova RN, Jasvantrai Desai P, Gibson FC, et al. Distinct proinflammatory host responses to Neisseria gonorrhoeae infection in immortalized human cervical and vaginal epithelial cells. Infect Immun 2001; 69: 5840-5848.
33. Reddy BS, Rastogi S, Das B, et al. Cytokine expression pattern in the genital tract of Chlamydia trachomatis positive infertile women-implication for T-cell responses. Clin Exp Immunol 2004; 137: 552-558.
34. Rebbapragada A, Wachihi C, Pettengell C, et al. Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract. AIDS 2007; 21: 589-598.
35. Mcgee ZA, Jensen RL, Clemens CM, et al. Gonococcal infection of human fallopian tube mucosa in organ culture: relationship of mucosal tissue TNF-α concentration to sloughing of ciliated cells. Sex Transm Dis 1999; 26: 160-165.
36. Svanborg C, Godaly G, Hedlund M. Cytokine responses during mucosal infections: role in disease pathogenesis and host defence. Curr Opin Microbiol 1999; 2: 99-105.
37. Parks KS, Dixon PB, Richey CM, et al. Spontaneous clearance of chlamydia trachomatis infection in untreated patients. Sex Transm Dis 1997; 24: 229-235.
38. Golden MR, Schillinger JA, Markowitz L, et al. Duration of untreated genital infections with chlamydia trachomatis: a review of the literature. Sex Transm Dis 2000; 27: 329-337.
39. Houlihan CF, Larke NL, Watson-Jones D, et al. HPV infection and increased risk of HIV acquisition. A systematic review and meta-analysis. AIDS 2012; 26: 10.
40. Masese L, Baeten JM, Richardson BA, et al. Changes in the contribution of genital tract infections to HIV acquisition among Kenyan high-risk women from 1993 to 2012. AIDS 2015; 29: 1077-1085. The analysis calculated the population risk attributable of various STIs to HIV incidence, and found HSV-2 and bacterial vaginosis to be the biggest players through time.
41. Zhu J, Hladik F, Woodward A, et al. Persistence of HIV-1 receptor-positive cells after HSV-2 reactivation is a potential mechanism for increased HIV-1 acquisition. Nature Med 2009; 15: 886-892.
42. Johnson LF, Dorrington RE, Bradshaw D, et al. The role of sexually transmitted infections in the evolution of the South African HIV epidemic. Trop Med Int Health 2012; 17: 161-168.
43. Eschenbach DA, Davick PR, Williams BL, et al. Prevalence of hydrogen peroxide-producing Lactobacillus species in normal women and women with bacterial vaginosis. J Clin Microbiol 1989; 27: 251-256.
44. Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med 2005; 353: 1899-1911.
45. Srinivasan S, Liu C, Mitchell CM, et al. Temporal variability of human vaginal bacteria and relationship with bacterial vaginosis. PLoS One 2010; 5: e10197.
46. Gajer P, Brotman RM, Bai G, et al. Temporal dynamics of the human vaginal microbiota. Sci Transl Med 2012; 4: 132ra152.
47. Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A 2011; 108: 4680-4687.
48. Spurbeck RR, Arvidson CG. Lactobacilli at the front line of defense against vaginally acquired infections. Future Microbiol 2011; 6: 567-582.
49. van de Wijgert JH, Verwijs MC, Turner AN, et al. Bacterial vaginosis and vaginal yeast, but not vaginal cleansing, increase HIV-1 acquisition in African women. J AIDS 2008; 48: 203-210.
50. Mirmonsef P, Krass L, Landay A, et al. The role of bacterial vaginosis and trichomonas in HIV transmission across the female genital tract. Current HIV Res 2012; 10: 202.
51. Myer L, Denny L, Telerant R, et al. Bacterial vaginosis and susceptibility to HIV infection in South African women: a nested case-control study. J Infect Dis 2005; 192: 1372-1380.
52. Myer L, Kuhn L, Stein ZA, et al. Intravaginal practices, bacterial vaginosis, and women's susceptibility to HIV infection: epidemiological evidence and biological mechanisms. Lancet Infect Dis 2005; 5: 786-794.
53. Madan RP, Masson L, Tugetman J, et al. Innate antibacterial activity in female genital tract secretions is associated with increased risk of HIV acquisition. AIDS Res Hum Retroviruses 2015; Epub ahead of print: DOI: 10.1089/aid.2015.0011.
54. Borgdorff H, Gautam R, Armstrong SD, et al. Cervicovaginal microbiome dysbiosis is associated with proteome changes related to alterations of the cervicovaginal mucosal barrier. Mucosal Immunol 2015; ePub ahead of print: DOI: 10: 1038/mi.2015.86.
55. Atarashi K, Tanoue T, Shima T, et al. Induction of colonic regulatory T cells by indigenous Clostridium species. Science 2011; 331: 337-341.
56. Round JL, Mazmanian SK. Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota. Proc Natl Acad Sci U S A 2010; 107: 12204-12209.
57. Libby EK, Pascal KE, Mordechai E, et al. Atopobium vaginae triggers an innate immune response in an in vitro model of bacterial vaginosis. Microbes Infect 2008; 10: 439-446.
58. Doerflinger SY, Throop AL, Herbst-Kralovetz MM. Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner. J Infect Dis 2014; 209: 1989-1999.
59. Kyongo JK, Jespers V, Goovaerts O, et al. Searching for lower female genital tract soluble and cellular biomarkers: defining levels and predictors in a cohort of healthy Caucasian women. PLoS One 2012; 7: e43951.
60. Deese J, Masson L, Miller W, et al. Injectable progestin-only contraception is associated with increased levels of pro-inflammatory cytokines in the female genital tract. Am J Reprod Immunol 2015; 74: 357-367.
61. Myer L, Denny L, Wright TC, et al. Prospective study of hormonal contraception and women's risk of HIV infection in South Africa. Int J Epidemiol 2007; 36: 166-174.
62. Heffron R, Donnell D, Rees H, et al. Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study. Lancet Infect Dis 2012; 12: 19-26.
63. Marx PA, Spira AI, Gettie A, et al. Progesterone implants enhance SIV vaginal transmission and early virus load. Nature Med 1996; 2: 1084-1089.
64. Sodora DL, Gettie A, Miller CJ, et al. Vaginal transmission of SIV: assessing infectivityand hormonal influences inmacaques inoculated with cell-free and cellassociated viral stocks. AIDS Res Hum Retroviruses 1998; 14: S119-S123.
65. Smith SM, Mefford M, Sodora D, et al. Topical estrogen protects against SIV vaginal transmission without evidence of systemic effect. AIDS 2004; 18: 1637-1643.
66. Miller L, Patton DL, Meier A, et al. Depomedroxyprogesterone-induced hypoestrogenism and changes in vaginal flora and epithelium. Obstet Gynecol 2000; 96: 431-439.
67. Critchlow CW, Wlner-Hanssen P, Eschenbach DA, et al. Determinants of cervical ectopia and of cervicitis: age, oral contraception, specific cervical infection, smoking, and douching. Am J Obstet Gynecol 1995; 173: 534-543.
68. Baeten JM, Nyange PM, Richardson BA, et al. Hormonal contraception and risk of sexually transmitted disease acquisition: results from a prospective study. Am J Obstet Gynecol 2001; 185: 380-385.
69. Morrison CS, Bright P, Wong EL, et al. Hormonal contraceptive use, cervical ectopy, and the acquisition of cervical infections. Sex Transm Dis 2004; 31: 561-567.
70. Pettifor A, Delaney S, Kleinschmidt I, et al. Use of injectable progestin contraception and risk of STI among South African women. Contraception 2009; 80: 555-560.
71. Ildgruben AK, Sjoberg IM, Hammarstrom ML. Influence of hormonal contraceptives on the immune cells and thickness of human vaginal epithelium. Obstet Gynecol 2003; 102: 571-582.
72. Ghanem KG, Shah N, Klein RS, et al. Influence of sex hormones, HIV status, and concomitant sexually transmitted infection on cervicovaginal inflammation. J Infect Dis 2005; 191: 358-366.
73. Chandra N, Thurman AR, Anderson S, et al. Depot medroxyprogesterone acetate increases immune cell numbers and activation markers in human vaginal mucosal tissues. AIDS Res Hum Retroviruses 2013; 29: 592-601.
74. Huijbregts RP, Helton ES, Michel KG, et al. Hormonal contraception and HIV- 1 infection: medroxyprogesterone acetate suppresses innate and adaptive immune mechanisms. Endocrinol 2013; 154: 1282-1295.
75. Prakash M, Patterson S, Kapembwa MS. Hormonal upregulation of CCR5 expression on T lymphocytes as a possible mechanism for increased HIV-1 risk. JAIDS 2005; 38: S14-S16.
76. Prakash M, Kapembwa MS, Gotch F, et al. Oral contraceptive use induces upregulation of the CCR5 chemokine receptor on CD4(+) T cells in the cervical epithelium of healthy women. J Reprod Immunol 2002; 54: 117-131.
77. Zang YC, Halder JB, Hong J, et al. Regulatory effects of estriol on T cell migration and cytokine profile: inhibition of transcription factor NF-kappa B. J Neuroimmunol 2002; 124: 106-114.
78. Ngcapu S, Masson L, Sibeko S, et al. Lower concentrations of chemotactic cytokines and soluble innate factors in the lower female genital tract associated with the use of injectable hormonal contraceptive. J Reprod Immunol 2015; 110: 14-21.
79. Scholes D, Daling JR, Stergachis A, et al. Vaginal douching as a risk factor for acute pelvic inflammatory disease. Obstet Gynecol 1993; 81: 601-606.
80. Sharkey DJ, Tremellen KP, Jasper MJ, et al. Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus. J Immunol 2012; 188: 2445-2454.
81. Fichorova RN, Tucker LD, Anderson DJ. The molecular basis of nonoxynol-9- induced vaginal inflammation and its possible relevance to human immunodeficiency virus type 1 transmission. J Infect Dis 2001; 184: 418-428.
82. Kleppa E, Ramsuran V, Zulu S, et al. Effect of female genital schistosomiasis and antischistosomal treatment on monocytes, CD4+ T-cells and CCR5 expression in the female genital tract. PLoS One 2014; 9: e98593.
83. Zabaleta J, Schneider BG, Ryckman K, et al. Ethnic differences in cytokine gene polymorphisms: potential implications for cancer development. Cancer Immunol Immunother 2008; 57: 107-114.
84. World Health Organization. 2003. Guidelines for the management of sexually transmitted infections. http://www.who.int/hiv/pub/sti/en/STIGuidelines2003. pdf. [Accessed 15 October 2015]
85. Wilkinson D, Abdool Karim SS, Harrison A, et al. Unrecognized sexually transmitted infections in rural South African women: a hidden epidemic. Bull World Health Organ 1999; 77: 22-28.
86. Celum C, Wald A, Hughes J, et al. Effect of aciclovir on HIV-1 acquisition in herpes simplex virus 2 seropositive women and men who have sex with men: a randomised, double-blind, placebo-controlled trial. Lancet 2008; 371: 2109-2119.
87. Gray RH, Wawer MJ, Brookmeyer R, et al. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 2001; 357: 1149-1153.
88. Kaul R, Kimani J, Nagelkerke NJ, et al. Monthly antibiotic chemoprophylaxis and incidence of sexually transmitted infections and HIV-1 infection in Kenyan sex workers: a randomized controlled trial. JAMA 2004; 291: 2555-2562.
89. Watson-Jones D, Weiss HA, Rusizoka M, et al. Effect of herpes simplex suppression on incidence of HIV among women in Tanzania. New Engl J Med 2008; 358: 1560-1571.
90. Wawer MJ, Sewankambo NK, Serwadda D, et al. Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Lancet 1999; 353: 525-535.
91. Grosskurth H, Todd J, Mwijarubi E, et al. Impact of improved treatment of sexually transmitted diseases on HIV infection in rural Tanzania: randomised controlled trial. Lancet 1995; 346: 530-536.
92. Grosskurth H, Gray R, Hayes R, et al. Control of sexually transmitted diseases for HIV-1 prevention: understanding the implications of the Mwanza and Rakai trials. Lancet 2000; 355: 1981-1987.
93. Gregson S, Adamson S, Papaya S, et al. Impact and process evaluation of integrated community and clinic-based HIV-1 control: a cluster-randomised trial in eastern Zimbabwe. PLoS Med 2007; 4: e102.
94. Kamali A, Quigley M, Nakiyingi J, et al. Syndromic management of sexuallytransmitted infections and behaviour change interventions on transmission of HIV-1 in rural Uganda: a community randomised trial. Lancet 2003; 361: 645-652.
95. Barnabas RV, Celum C. Infectious co-factors in HIV-1 transmission herpes simplex virus type-2 and HIV-1: new insights and interventions. Current HIV research 2012; 10: 228.
96. Barrons R, Tassone D. Use of Lactobacillus probiotics for bacterial genitourinary infections in women: a review. Clin Ther 2008; 30: 453-468.