Immunobiology of Genital Tract Trauma: Endocrine Regulation of HIV Acquisition in Women Following Sexual Assault or Genital Tract Mutilation

American Journal of Reproductive Immunology

Volumn 69, Issue SUPPL.1, 2013, Pages 51-60

  Ghosh, Mimi ^a   Rodriguez Garcia, Marta ^b   Wira, Charles R ^b  

^a GEORGE WASHINGTON UNIVERSITY   (United States)

^b DARTMOUTH MEDICAL SCHOOL   (United States)

Author keywords

Adaptive immunity; Female genital mutilation; Female reproductive tract; HIV; Immune cells; Innate immunity; Window of vulnerability sexual trauma

Indexed keywords

CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR4; ESTRADIOL; FOLLITROPIN; LUTEINIZING HORMONE; ORAL CONTRACEPTIVE AGENT; TOLL LIKE RECEPTOR 3; TOLL LIKE RECEPTOR 4;

ADOLESCENCE; ANTIGEN PRESENTING CELL; AUTOMUTILATION; CD8+ T LYMPHOCYTE; CORPUS LUTEUM; CYTOTOXIC T LYMPHOCYTE; ENDOMETRIUM; FEMALE GENITAL SYSTEM; GENITAL INJURY; GYNECOLOGIC DISEASE; HIGH RISK BEHAVIOR; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HUMORAL IMMUNITY; IMMUNOBIOLOGY; INNATE IMMUNITY; LIFE CYCLE; LUTEINIZING HORMONE RELEASE; MENOPAUSE; MENSTRUAL CYCLE; MICROENVIRONMENT; PREGNANCY; PRIORITY JOURNAL; PUBERTY; REVIEW; RISK FACTOR; SEXUAL CRIME; SEXUAL INTERCOURSE; SEXUAL TRANSMISSION; SEXUALLY TRANSMITTED DISEASE; UPREGULATION; UTERINE TUBE; VAGINA EPITHELIUM; VIRUS REPLICATION; VIRUS TRANSMISSION;

ADOLESCENT; ADULT; COITUS; FEMALE; GENITALIA, FEMALE; HIV INFECTIONS; HUMANS; MALE; MIDDLE AGED; PREGNANCY; RAPE; UNSAFE SEX;

EID: 84873463205     PISSN: 10467408     EISSN: 16000897     Source Type: Journal    
DOI: 10.1111/aji.12027     Document Type: Review

References (96)

1. WHO: Progress report 2011: global HIV/AIDS response, 2011.
2. UNAIDS: Fact sheet: adolescents, young people and HIV, 2012.
3. Garcia-Moreno C, Watts C: Violence against women: its importance for HIV/AIDS. AIDS 2000; 14(Suppl 3):S253-S265.
4. Krug EG, Mercy JA, Dahlberg LL, Zwi AB: The world report on violence and health. Lancet 2002; 360:1083-1088.
5. WHO: Sexual and reproductive health of women living with HIV/AIDS, 2006.
6. CDC: Basic information about HIV and AIDS, 2010.
7. Galvin SR, Cohen MS: The role of sexually transmitted diseases in HIV transmission. Nat Rev Microbiol 2004; 2:33-42.
8. Gray RH, Wawer MJ, Serwadda D, Sewankambo N, Li C, Wabwire-Mangen F, Paxton L, Kiwanuka N, Kigozi G, Konde-Lule J, Quinn TC, Gaydos CA, McNairn D: Population-based study of fertility in women with HIV-1 infection in Uganda. Lancet 1998; 351:98-103.
9. Hunter SC, Isingo R, Boerma JT, Urassa M, Mwaluko GM, Zaba B: The association between HIV and fertility in a cohort study in rural Tanzania. J Biosoc Sci 2003; 35:189-199.
10. Ross A, Van der Paal L, Lubega R, Mayanja BN, Shafer LA, Whitworth J: HIV-1 disease progression and fertility: the incidence of recognized pregnancy and pregnancy outcome in Uganda. AIDS 2004; 18:799-804.
11. Mallet J, Kalambi V: Coerced and forced sterilization of HIV-positive women in Namibia. HIV AIDS Policy Law Rev 2008; 13:77-78.
12. NIJCDC: Full report of the prevalence, incidence, and consequences of violence against women, 2000.
13. WHO: World report on violence and health, 2002.
14. CDC: Sexual violence, 2008.
15. Deribe K, Woldemichael K, Bernard N, Yakob B: Gender difference in HIV status disclosure among HIV positive service users. East Afr J Public Health 2009; 6:248-255.
16. Rujumba J, Neema S, Byamugisha R, Tylleskar T, Tumwine JK, Heggenhougen HK: 'Telling my husband I have HIV is too heavy to come out of my mouth': pregnant women's disclosure experiences and support needs following antenatal HIV testing in eastern Uganda. J Int AIDS Soc 2012; 15:17429.
17. Ochiel DO, Fahey JV, Ghosh M, Haddad SN, Wira CR: Innate immunity in the female reproductive tract: role of sex hormones in regulating uterine epithelial cell protection against pathogens. Curr Womens Health Rev 2008; 4:102-117.
18. Wira CR, Fahey JV, Sentman CL, Pioli PA, Shen L: Innate and adaptive immunity in female genital tract: cellular responses and interactions. Immunol Rev 2005; 206:306-335.
19. Fahey JV, Wright JA, Shen L, Smith JM, Ghosh M, Rossoll RM, Wira CR: Estradiol selectively regulates innate immune function by polarized human uterine epithelial cells in culture. Mucosal Immunol 2008; 1:317-325.
20. Heldring N, Pike A, Andersson S, Matthews J, Cheng G, Hartman J, Tujague M, Strom A, Treuter E, Warner M, Gustafsson JA: Estrogen receptors: how do they signal and what are their targets. Physiol Rev 2007; 87:905-931.
21. Hickey DK, Patel MV, Fahey JV, Wira CR: Innate and adaptive immunity at mucosal surfaces of the female reproductive tract: stratification and integration of immune protection against the transmission of sexually transmitted infections. J Reprod Immunol 2011; 88:185-194.
22. Wira CR, Patel MV, Ghosh M, Mukura L, Fahey JV: Innate immunity in the human female reproductive tract: endocrine regulation of endogenous antimicrobial protection against HIV and other sexually transmitted infections. Am J Reprod Immunol 2011; 65:196-211.
23. Ghosh M, Fahey JV, Shen Z, Lahey T, Cu-Uvin S, Wu Z, Mayer K, Wright PF, Kappes JC, Ochsenbauer C, Wira CR: Anti-HIV activity in cervical-vaginal secretions from HIV-positive and -negative women correlate with innate antimicrobial levels and IgG antibodies. PLoS ONE 2010; 5:e11366.
24. Wira CR, Fahey JV: A new strategy to understand how HIV infects women: identification of a window of vulnerability during the menstrual cycle. AIDS 2008; 22:1909-1917.
25. Hwang LY, Scott ME, Ma Y, Moscicki AB: Higher levels of cervicovaginal inflammatory and regulatory cytokines and chemokines in healthy young women with immature cervical epithelium. J Reprod Immunol 2011; 88:66-71.
26. Madan RP, Carpenter C, Fiedler T, Kalyoussef S, McAndrew TC, Viswanathan S, Kim M, Keller MJ, Fredricks DN, Herold BC: Altered biomarkers of mucosal immunity and reduced vaginal lactobacillus concentrations in sexually active female adolescents. PLoS ONE 2012; 7:e40415.
27. Jones JS, Rossman L, Hartman M, Alexander CC: Anogenital injuries in adolescents after consensual sexual intercourse. Acad Emerg Med 2003; 10:1378-1383.
28. Jones JS, Rossman L, Wynn BN, Dunnuck C, Schwartz N: Comparative analysis of adult versus adolescent sexual assault: epidemiology and patterns of anogenital injury. Acad Emerg Med 2003; 10:872-877.
29. Hirbod T, Kaldensjo T, Broliden K: In situ distribution of HIV-binding CCR5 and C-type lectin receptors in the human endocervical mucosa. PLoS ONE 2011; 6:e25551.
30. Mayer KH, Anderson DJ: Heterosexual HIV transmission. Infect Agents Dis 1995; 4:273-284.
31. Moss GB, Clemetson D, D'Costa L, Plummer FA, Ndinya-Achola JO, Reilly M, Holmes KK, Piot P, Maitha GM, Hillier SL, Kiviat NC, Cameron CW, Wamola IA, Kreiss JK: Association of cervical ectopy with heterosexual transmission of human immunodeficiency virus: results of a study of couples in Nairobi, Kenya. J Infect Dis 1991; 164:588-591.
32. Wira CR, Fahey JV, White HD, Yeaman GR, Given AL, Howell AL: The mucosal immune system in the human female reproductive tract: influence of stage of the menstrual cycle and menopause on mucosal immunity in the uterus. In The Endometrium, S Glasser, J Aplin, L Guidice, S Tabibzadeh (eds). New York, Taylor and Francis, 2002, pp 371-404.
33. + CTL activity within the human female reproductive tract: influence of stage of the menstrual cycle and menopause. J Immunol 1997; 158:3017-3027.
34. White HD, Musey LK, Andrews MM, Yeaman GR, DeMars LR, Manganiello PD, Howell AL, Wira CR, Green WR, McElrath MJ: Human immunodeficiency virus-specific and CD3-redirected cytotoxic T lymphocyte activity in the human female reproductive tract: lack of correlation between mucosa and peripheral blood. J Infect Dis 2001; 183:977-983.
35. Sato K, Kawasaki H, Nagayama H, Enomoto M, Morimoto C, Tadokoro K, Juji T, Takahashi TA: TGF-beta 1 reciprocally controls chemotaxis of human peripheral blood monocyte-derived dendritic cells via chemokine receptors. J Immunol 2000; 164:2285-2295.
36. Casslén B, Sandberg T, Gustavsson B, Willén R, Nilbert M: Transforming growth factor beta1 in the human endometrium. Cyclic variation, increased expression by estradiol and progesterone, and regulation of plasminogen activators and plasminogen activator inhibitor-1. Biol Reprod 1998; 58:1343-1350.
37. Vishwanathan SA, Guenthner PC, Lin CY, Dobard C, Sharma S, Adams DR, Otten RA, Heneine W, Hendry RM, McNicholl JM, Kersh EN: High susceptibility to repeated, low-dose, vaginal SHIV exposure late in the luteal phase of the menstrual cycle of pigtail macaques. J Acquir Immune Defic Syndr 2011; 57:261-264.
38. Slaughter L, Brown CR, Crowley S, Peck R: Patterns of genital injury in female sexual assault victims. Am J Obstet Gynecol 1997; 176:609-616.
39. WHO: Intimate partner violence during pregnancy, 2011.
40. Mor G, Cardenas I, Abrahams V, Guller S: Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci 2011; 1221:80-87.
41. Ghartey JP, Carpenter C, Gialanella P, Rising C, McAndrew TC, Mhatre M, Tugetman J, Einstein MH, Chazotte C, Herold BC: Association of bactericidal activity of genital tract secretions with Escherichia coli colonization in pregnancy. Am J Obstet Gynecol 2012; in press.
42. Anderson BL, Ghosh M, Raker C, Fahey J, Song Y, Rouse DJ, Wira CR, Cu-Uvin S: In vitro anti-HIV-1 activity in cervicovaginal secretions from pregnant and nonpregnant women. Am J Obstet Gynecol 2012; 207:65 e61-10.
43. SASC: Sexual assault and the older woman. Available at: http://www.sascwr.org/files/www/resources_pdfs/sexual_assault/SEXUAL_ASSAULT_AND_THE_OLDER_WOMAN.pdf. Accessed September 27, 2012.
44. Gameiro CM, Romao F, Castelo-Branco C: Menopause and aging: changes in the immune system-a review. Maturitas 2010; 67:316-320.
45. Goetzl EJ, Huang MC, Kon J, Patel K, Schwartz JB, Fast K, Ferrucci L, Madara K, Taub DD, Longo DL: Gender specificity of altered human immune cytokine profiles in aging. FASEB J 2010; 24:3580-3589.
46. Rollenhagen C, Asin SN: Enhanced HIV-1 replication in ex vivo ectocervical tissues from post-menopausal women correlates with increased inflammatory responses. Mucosal Immunol 2011; 4:671-681.
47. Keller MJ, Guzman E, Hazrati E, Kasowitz A, Cheshenko N, Wallenstein S, Cole AL, Cole AM, Profy AT, Wira CR, Hogarty K, Herold BC: PRO 2000 elicits a decline in genital tract immune mediators without compromising intrinsic antimicrobial activity. AIDS 2007; 21:467-476.
48. Lahey T, Ghosh M, Fahey JV, Shen Z, Mukura LR, Song Y, Cu-Uvin S, Mayer KH, Wright PF, Kappes JC, Ochsenbauer C, Wira CR: Selective impact of HIV disease progression on the innate immune system in the human female reproductive tract. PLoS ONE 2012; 7:e38100.
49. + T cells and HIV susceptibility. Curr Opin HIV AIDS 2012; 7:195-202.
50. + T cells. Nature 2005; 434:1148-1152.
51. + T cells. Science 1999; 286:1353-1357.
52. + T cell subset coexpressing multiple markers of HIV susceptibility. J Immunol 2011; 187:6032-6042.
53. + T cells in healthy postmenopausal women. J Acquir Immune Defic Syndr 2012; 59:221-228.
54. Starkey PM, Clover LM, Rees MCP: Variation during the menstrual cycle of immune cell populations in human endometrium. Eur J Obstet Gynecol Reprod Biol 1991; 39:203-207.
55. Collins KB, Patterson BK, Naus GJ, Landers DV, Gupta P: Development of an in vitro organ culture model to study transmission of HIV-1 in the female genital tract. Nat Med 2000; 6:475-479.
56. Cummins Jr JE, Guarner J, Flowers L, Guenthner PC, Bartlett J, Morken T, Grohskopf LA, Paxton L, Dezzutti CS: Preclinical testing of candidate topical microbicides for anti-human immunodeficiency virus type 1 activity and tissue toxicity in a human cervical explant culture. Antimicrob Agents Chemother 2007; 51:1770-1779.
57. Greenhead P, Hayes P, Watts PS, Laing KG, Griffin GE, Shattock RJ: Parameters of human immunodeficiency virus infection of human cervical tissue and inhibition by vaginal virucides. J Virol 2000; 74:5577-5586.
58. Sharova N, Swingler C, Sharkey M, Stevenson M: Macrophages archive HIV-1 virions for dissemination in trans. EMBO J 2005; 24:2481-2489.
59. Altfeld M, Fadda L, Frleta D, Bhardwaj N: DCs and NK cells: critical effectors in the immune response to HIV-1. Nat Rev Immunol 2011; 11:176-186.
60. Liu K, Victora GD, Schwickert TA, Guermonprez P, Meredith MM, Yao K, Chu FF, Randolph GJ, Rudensky AY, Nussenzweig M: In vivo analysis of dendritic cell development and homeostasis. Science 2009; 324:392-397.
61. Randolph GJ, Ochando J, Partida-Sanchez S: Migration of dendritic cell subsets and their precursors. Annu Rev Immunol 2008; 26:293-316.
62. Wu L, KewalRamani VN: Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol 2006; 6:859-868.
63. Banchereau J, Steinman RM: Dendritic cells and the control of immunity. Nature 1998; 392:245-252.
64. Steinman RM, Hemmi H: Dendritic cells: translating innate to adaptive immunity. Curr Top Microbiol Immunol 2006; 311:17-58.
65. Iijima N, Linehan MM, Saeland S, Iwasaki A: Vaginal epithelial dendritic cells renew from bone marrow precursors. Proc Nat Acad Sci 2007; 104:19061-19066.
66. Iijima N, Linehan MM, Zamora M, Butkus D, Dunn R, Kehry MR, Laufer TM, Iwasaki A: Dendritic cells and B cells maximize mucosal Th1 memory response to herpes simplex virus. J Exp Med 2008; 205:3041-3052.
67. Schulke L, Manconi F, Markham R, Fraser IS: Endometrial dendritic cell populations during the normal menstrual cycle. Hum Reprod 2008; 23:1574-1580.
68. Cunningham AL, Donaghy H, Harman AN, Kim M, Turville SG: Manipulation of dendritic cell function by viruses. Curr Opin Microbiol 2010; 13:524-529.
69. Lambotin M, Raghuraman S, Stoll-Keller F, Baumert TF, Barth H: A look behind closed doors: interaction of persistent viruses with dendritic cells. Nat Rev Microbiol 2010; 8:350-360.
70. Chehimi J, Luo Q, Azzoni L, Shawver L, Ngoubilly N, June R, Jerandi G, Farabaugh M, Montaner LJ: HIV-1 transmission and cytokine-induced expression of DC-SIGN in human monocyte-derived macrophages. J Leukoc Biol 2003; 74:757-763.
71. Gringhuis SI, van der Vlist M, van den Berg LM, den Dunnen J, Litjens M, Geijtenbeek TBH: HIV-1 exploits innate signaling by TLR8 and DC-SIGN for productive infection of dendritic cells. Nat Immunol 2010; 11:419-426.
72. Rieger L, Honig A, Sütterlin M, Kapp M, Dietl J, Ruck P, Kämmerer U: Antigen-presenting cells in human endometrium during the menstrual cycle compared to early pregnancy. J Soc Gynecol Investig 2004; 11:488-493.
73. Ochiel DO, Ochsenbauer C, Kappes JC, Ghosh M, Fahey JV, Wira CR: Uterine epithelial cell regulation of DC-SIGN expression inhibits transmitted/founder HIV-1 trans infection by immature dendritic cells. PLoS ONE 2010; 5:e14306.
74. Ochiel DO, Ghosh M, Fahey JV, Guyre PM, Wira CR: Human uterine epithelial cell secretions regulate dendritic cell differentiation and responses to TLR ligands. J Leukoc Biol 2010; 88:435-444.
75. Rodriguez-Garcia M, Climent N, Oliva H, Casanova V, Franco R, Leon A, Gatell JM, Garcia F, Gallart T: Increased alpha-defensins 1-3 production by dendritic cells in HIV-infected individuals is associated with slower disease progression. PLoS ONE 2010; 5:e9436.
76. Escribese MM, Rodriguez-Garcia M, Sperling R, Engel SM, Gallart T, Moran TM: Alpha-defensins 1-3 release by dendritic cells is reduced by estrogen. Reprod Biol Endocrinol 2011; 9:118.
77. Rodriguez-Garcia M, Oliva H, Climent N, Garcia F, Gatell JM, Gallart T: Human immature monocyte-derived dendritic cells produce and secrete alpha-defensins 1-3. J Leukoc Biol 2007; 82:1143-1146.
78. de Witte L, Nabatov A, Pion M, Fluitsma D, de Jong MA, de Gruijl T, Piguet V, van Kooyk Y, Geijtenbeek TB: Langerin is a natural barrier to HIV-1 transmission by Langerhans cells. Nat Med 2007; 13:367-371.
79. Hladik F, Sakchalathorn P, Ballweber L, Lentz G, Fialkow M, Eschenbach D, McElrath MJ: Initial events in establishing vaginal entry and infection by human immunodeficiency virus type-1. Immunity 2007; 26:257-270.
80. Ballweber L, Robinson B, Kreger A, Fialkow M, Lentz G, McElrath MJ, Hladik F: Vaginal langerhans cells nonproductively transporting HIV-1 mediate infection of T cells. J Virol 2011; 85:13443-13447.
81. Chacko L, Ford N, Sbaiti M, Siddiqui R: Adherence to HIV post-exposure prophylaxis in victims of sexual assault: a systematic review and meta-analysis. Sex Transm Infect 2012; 88:335-341.
82. Speight CG, Klufio A, Kilonzo SN, Mbugua C, Kuria E, Bunn JE, Taegtmeyer M: Piloting post-exposure prophylaxis in Kenya raises specific concerns for the management of childhood rape. Trans R Soc Trop Med Hyg 2006; 100:14-18.
83. Bakhru A, Mallinger JB, Fox MC: Postexposure prophylaxis for victims of sexual assault: treatments and attitudes of emergency department physicians. Contraception 2010; 82:168-173.
84. Rose VL: ACOG issues report on sexual assault. American College of Obstetricians and Gynecologists. Am Fam Physician 1998; 57:1144-1145.
85. CDC: Sexual assault and STDs. Sexually transmitted diseases treatment guidelines, 2010.
86. McLean I, Roberts SA, White C, Paul S: Female genital injuries resulting from consensual and non-consensual vaginal intercourse. Forensic Sci Int 2011; 204:27-33.
87. Geist RF: Sexually related trauma. Emerg Med Clin North Am 1988; 6:439-466.
88. Lauber AA, Souma ML: Use of toluidine blue for documentation of traumatic intercourse. Obstet Gynecol 1982; 60:644-648.
89. Sommers MS: Defining patterns of genital injury from sexual assault: a review. Trauma Violence Abuse 2007; 8:270-280.
90. Stoecklein VM, Osuka A, Lederer JA: Trauma equals danger-damage control by the immune system. J Leukoc Biol 2012; 92:539-551.
91. McCann J, Miyamoto S, Boyle C, Rogers K: Healing of nonhymenal genital injuries in prepubertal and adolescent girls: a descriptive study. Pediatrics 2007; 120:1000-1011.
92. Ramin SM, Satin AJ, Stone Jr IC, Wendel Jr GD: Sexual assault in postmenopausal women. Obstet Gynecol 1992; 80:860-864.
93. Sugar NF, Fine DN, Eckert LO: Physical injury after sexual assault: findings of a large case series. Am J Obstet Gynecol 2004; 190:71-76.
94. Sommers MS, Zink T, Baker RB, Fargo JD, Porter J, Weybright D, Schafer JC: The effects of age and ethnicity on physical injury from rape. J Obstet Gynecol Neonatal Nurs 2006; 35:199-207.
95. Dave AJ, Sethi A, Morrone A: Female genital mutilation: what every American dermatologist needs to know. Dermatol Clin 2011; 29:103-109.
96. Morrone A, Hercogova J, Lotti T: Stop female genital mutilation: appeal to the international dermatologic community. Int J Dermatol 2002; 41:253-263.