Role of Semen in Modulating the Female Genital Tract Microenvironment - Implications for HIV Transmission

American Journal of Reproductive Immunology

Volumn 71, Issue 6, 2014, Pages 564-574

  Doncel, Gustavo F ^a   Anderson, Sharon ^a   Zalenskaya, Irina ^a  

^a EASTERN VIRGINIA MEDICAL SCHOOL   (United States)

Author keywords

HIV; Semen; Vaginal inflammation; Vaginal innate immunity

Indexed keywords

CHEMOKINE RECEPTOR CCR6; INTERLEUKIN 7; MACROPHAGE INFLAMMATORY PROTEIN 3ALPHA; PROSTAGLANDIN E; RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KAPPA B; TOLL LIKE RECEPTOR; TRANSCRIPTION FACTOR; CCL20 PROTEIN, HUMAN; CCR6 PROTEIN, HUMAN; IL7 PROTEIN, HUMAN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

ARTICLE; CELL ACTIVATION; CONCEPTION; DISEASE TRANSMISSION; FEMALE GENITAL SYSTEM; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IMMUNE RESPONSE; IMMUNE SYSTEM; IMMUNOMODULATION; INFECTION SENSITIVITY; INFLAMMATION; MICROENVIRONMENT; NONHUMAN; PREGNANCY; PRIORITY JOURNAL; SEXUAL INTERCOURSE; SEXUAL TRANSMISSION; SPERM; TARGET CELL; UPREGULATION; UTERINE CERVIX; VAGINA; VIRUS REPLICATION; BIOSYNTHESIS; CD4+ T LYMPHOCYTE; COITUS; DISEASE PREDISPOSITION; FEMALE; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; MALE; MUCOSA; TRANSMISSION; TUMOR MICROENVIRONMENT; VIROLOGY;

CD4-POSITIVE T-LYMPHOCYTES; CELLULAR MICROENVIRONMENT; CERVIX UTERI; CHEMOKINE CCL20; COITUS; DISEASE SUSCEPTIBILITY; FEMALE; HIV INFECTIONS; HUMANS; INFLAMMATION; INTERLEUKIN-7; MALE; MUCOUS MEMBRANE; NF-KAPPA B; PROSTAGLANDINS E; RECEPTORS, CCR6; SEMEN; TRANSFORMING GROWTH FACTOR BETA; VAGINA;

EID: 84900822061     PISSN: 10467408     EISSN: 16000897     Source Type: Journal    
DOI: 10.1111/aji.12231     Document Type: Article

References (127)

1. Robertson SA: Seminal plasma and male factor signalling in the female reproductive tract. Cell Tissue Res 2005; 322:43-52.
2. Schuberth HJ, Taylor U, Zerbe H, Waberski D, Hunter R, Rath D: Immunological responses to semen in the female genital tract. Theriogenology 2008; 70:1174-1181.
3. UNAIDS: Global Report: UNAIDS Report on the Global AIDS Epidemic. Geneva, UNAIDS, 2013.
4. WHO: Women's Health Fact Sheet No. 334. Geneva, WHO, 2013.
5. Shattock RJ, Moore JP: Inhibiting sexual transmission of HIV-1 infection. Nat Rev Microbiol 2003; 1:25-34.
6. Gray RH, Wawer MJ, Brookmeyer R, Sewankambo NK, Serwadda D, Wabwire-Mangen F, Lutalo T, Li X, vanCott T, Quinn TC: Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet 2001; 357:1149-1153.
7. Hughes JP, Baeten JM, Lingappa JR, Magaret AS, Wald A, de Bruyn G, Kiarie J, Inambao M, Kilembe W, Farquhar C, Celum C: Determinants of per-coital-act HIV-1 infectivity among African HIV-1-serodiscordant couples. J Infect Dis 2012; 205:358-365.
8. Wawer MJ, Gray RH, Sewankambo NK, Serwadda D, Li X, Laeyendecker O, Kiwanuka N, Kigozi G, Kiddugavu M, Lutalo T, Nalugoda F, Wabwire-Mangen F, Meehan MP, Quinn TC: Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J InfectDis 2005; 191:1403-1409.
9. Boily MC, Baggaley RF, Wang L, Masse B, White RG, Hayes RJ, Alary M: Heterosexual risk of HIV-1 infection per sexual act: systematic review and meta-analysis of observational studies. Lancet Infect Dis 2009; 9:118-129.
10. Galvin SR, Cohen MS: The role of sexually transmitted diseases in HIV transmission. Nat Rev Microbiol 2004; 2:33-42.
11. Pilcher CD, Tien HC, Eron JJ Jr, Vernazza PL, Leu SY, Stewart PW, Goh LE, Cohen MS: Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis 2004; 189:1785-1792.
12. Hladik F, Doncel GF: Preventing mucosal HIV transmission with topical microbicides: challenges and opportunities. Antiviral Res 2010; 88 (Suppl 1):S3-S9.
13. Robertson SA: Seminal fluid signaling in the female reproductive tract: lessons from rodents and pigs. J Anim Sci 2007; 85:E36-E44.
14. Sharkey DJ, Macpherson AM, Tremellen KP, Robertson SA: Seminal plasma differentially regulates inflammatory cytokine gene expression in human cervical and vaginal epithelial cells. Mol Hum Reprod 2007; 13:491-501.
15. Robertson SA, Guerin LR, Moldenhauer LM, Hayball JD: Activating T regulatory cells for tolerance in early pregnancy - the contribution of seminal fluid. J Reprod Immunol 2009; 83:109-116.
16. Joseph T, Zalenskaya IA, Sawyer LC, Chandra N, Doncel GF: Seminal plasma induces prostaglandin-endoperoxide synthase (PTGS) 2 expression in immortalized human vaginal cells: involvement of semen prostaglandin E2 in PTGS2 upregulation. Biol Reprod 2013; 88:13.
17. Doncel GF, Joseph T, Thurman AR: Role of semen in HIV-1 transmission: inhibitor or facilitator? Am J Reprod Immunol 2011; 65:292-301.
18. + T cells and HIV susceptibility. Curr Opin HIV AIDS 2012; 7:195-202.
19. Hladik F, McElrath MJ: Setting the stage: host invasion by HIV. Nat Rev Immunol 2008; 8:447-457.
20. Pudney J, Quayle AJ, Anderson DJ: Immunological microenvironments in the human vagina and cervix: mediators of cellular immunity are concentrated in the cervical transformation zone 1. Biol Reprod 2005; 73:1253-1263.
21. Kaushic C: HIV-1 infection in the female reproductive tract: role of Interactions between HIV-1 and genital epithelial cells. Am J Reprod Immunol 2011; 65:253-260.
22. Norvell MK, Benrubi GI, Thompson RJ: Investigation of microtrauma after sexual intercourse. J Reprod Med 1984; 29:269-271.
23. Prakash M, Patterson S, Gotch F, Kapembwa MS: Recruitment of CD4 T lymphocytes and macrophages into the cervical epithelium of women after coitus. Am J Obstet Gynecol 2003; 188:376-381.
24. 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.
25. Li Q, Estes JD, Schlievert PM, Duan L, Brosnahan AJ, Southern PJ, Reilly CS, Peterson ML, Schultz-Darken N, Brunner KG, Nephew KR, Pambuccian S, Lifson JD, Carlis JV, Haase AT: Glycerol monolaurate prevents mucosal SIV transmission. Nature 2009; 458:1034-1038.
26. Micsenyi AM, Zony C, Alvarez RA, Durham ND, Chen BK, Klotman ME: Postintegration HIV-1 infection of cervical epithelial cells mediates contact-dependent productive infection of T cells. J Infect Dis 2013; 208:1756-1767.
27. 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.
28. Shey MS, Garrett NJ, McKinnon LR, Passmore JA: The role of dendritic cells in driving genital tract inflammation and HIV transmission risk: are there opportunities to intervene? Innate Immun 2013; [Epub ahead of print].
29. Wang JH, Janas AM, Olson WJ, Wu L: Functionally distinct transmission of human immunodeficiency virus type 1 mediated by immature and mature dendritic cells. J Virol 2007; 81:8933-8943.
30. Hu J, Gardner MB, Miller CJ: Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J Virol 2000; 74:6087-6095.
31. Hladik F, Hope TJ: HIV infection of the genital mucosa in women. Curr HIV/AIDS Rep 2009; 6:20-28.
32. 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.
33. Miller CJ, Li Q, Abel K, Kim EY, Ma ZM, Wietgrefe S, La Franco-Scheuch L, Compton L, Duan L, Shore MD, Zupancic M, Busch M, Carlis J, Wolinsky S, Haase AT: Propagation and dissemination of infection after vaginal transmission of simian immunodeficiency virus. J Virol 2005; 79:9217-9227.
34. Carias AM, McCoombe S, McRaven M, Anderson M, Galloway N, Vandergrift N, Fought AJ, Lurain J, Duplantis M, Veazey RS, Hope TJ: Defining the interaction of HIV-1 with the mucosal barriers of the female reproductive tract. J Virol 2013; 87:11388-11400.
35. Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, Sun C, Grayson T, Wang S, Li H, Wei X, Jiang C, Kirchherr JL, Gao F, Anderson JA, Ping LH, Swanstrom R, Tomaras GD, Blattner WA, Goepfert PA, Kilby JM, Saag MS, Delwart EL, Busch MP, Cohen MS, Montefiori DC, Haynes BF, Gaschen B, Athreya GS, Lee HY, Wood N, Seoighe C, Perelson AS, Bhattacharya T, Korber BT, Hahn BH, Shaw GM: Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci U S A 2008; 105:7552-7557.
36. Haase AT: Early events in sexual transmission of HIV and SIV and opportunities for interventions. Annu Rev Med 2010; 62:127-139.
37. Haaland RE, Hawkins PA, Salazar-Gonzalez J, Johnson A, Tichacek A, Karita E, Manigart O, Mulenga J, Keele BF, Shaw GM, Hahn BH, Allen SA, Derdeyn CA, Hunter E: Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1. PLoS Pathog 2009; 5:e1000274.
38. Sharkey DJ, Tremellen KP, Jasper MJ, Gemzell-Danielsson K, Robertson SA: Seminal fluid induces leukocyte recruitment and cytokine and chemokine mRNA expression in the human cervix after coitus. J Immunol 2012; 188:2445-2454.
39. Balandya E, Wieland-Alter W, Sanders K, Lahey T: Human seminal plasma fosters CD4(+) regulatory T-cell phenotype and transforming growth factor-beta1 expression. Am J Reprod Immunol 2012; 68:322-330.
40. Eschenbach DA, Patton DL, Hooton TM, Meier AS, Stapleton A, Aura J, Agnew K: Effects of vaginal intercourse with and without a condom on vaginal flora and vaginal epithelium. J Infect Dis 2001; 183:913-918.
41. Astrup BS, Ravn P, Lauritsen J, Thomsen JL: Nature, frequency and duration of genital lesions after consensual sexual intercourse-implications for legal proceedings. Forensic Sci Int 2012; 219:50-56.
42. Jones JS, Rossman L, Hartman M, Alexander CC: Anogenital injuries in adolescents after consensual sexual intercourse. Acad Emerg Med 2003; 10:1378-1383.
43. Ghosh M, Rodriguez-Garcia M, Wira CR: Immunobiology of genital tract trauma: endocrine regulation of HIV acquisition in women following sexual assault or genital tract mutilation. Am J Reprod Immunol 2013; 69 (Suppl 1):51-60.
44. Berman JR, Bassuk J: Physiology and pathophysiology of female sexual function and dysfunction. World J Urol 2002; 20:111-118.
45. Barnhart KT, Pretorius ES, Timbers K, Shera D, Shabbout M, Malamud D: In vivo distribution of a vaginal gel: MRI evaluation of the effects of gel volume, time and simulated intercourse. Contraception 2004; 70:498-505.
46. Barnhart K, Kulp JL, Rosen M, Shera DM: A randomized trial to determine the distribution of four topical gel formulations in the human vagina. Contraception 2009; 79:297-303.
47. Schwebke JR, Venglarik MF, Morgan SC: Delayed versus immediate bedside inoculation of culture media for diagnosis of vaginal trichomonosis. J Clin Microbiol 1999; 37:2369-2370.
48. Mitchell C, Manhart LE, Thomas KK, Agnew K, Marrazzo JM: Effect of sexual activity on vaginal colonization with hydrogen peroxide-producing lactobacilli and Gardnerella vaginalis. Sex Transm Dis 2011; 38:1137-1144.
49. Martin HL, 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.
50. Baeten J, Hassan W, Chohan V, Richardson BA, Mandaliya K, Ndinya-Achola JO, Jaoko W, McClelland RS: Prospective study of correlates of vaginal Lactobacillus colonization among high-risk HIV-1 seronegative women. Sex Transm Infect 2009; 85:348-353.
51. Newton ER, Piper JM, Shain RN, Perdue ST, Peairs W: Predictors of the vaginal microflora. Am J Obstet Gynecol 2001; 184:845-853 discussion 53-55.
52. Ma L, Lv Z, Su J, Wang J, Yan D, Wei J, Pei S: Consistent condom use increases the colonization of Lactobacillus crispatus in the vagina. PLoS One 2013; 8:e70716.
53. Sabatte J, Lenicov FR, Cabrini M, Rodriguez Rodrigues C, Ostrowski M, Ceballos A, Amigorena S, Geffner J: The role of semen in sexual transmission of HIV: beyond a carrier for virus particles. Microbes Infect 2011; 13:977-982.
54. O'Connor TJ, Kinchington D, Kangro HO, Jeffries DJ: The activity of candidate virucidal agents, low pH and genital secretions against HIV-1 in vitro. Int J STD AIDS 1995; 6:267-272.
55. Martellini JA, Cole AL, Venkataraman N, Quinn GA, Svoboda P, Gangrade BK, Pohl J, Sørensen OE, Cole AM: Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma. FASEB J 2009; 23:3609-3618.
56. Agarwal A, Prabakaran SA: Mechanism, measurement, and prevention of oxidative stress in male reproductive physiology. Indian J Exp Biol 2005; 43:963-974.
57. + T cells mediated by DC-SIGN. J Virol 2007; 81:13723-13734.
58. Stax MJ, van Montfort T, Sprenger RR, Melchers M, Sanders RW, van Leeuwen E, Repping S, Pollakis G, Speijer D, Paxton WA: Mucin 6 in seminal plasma binds DC-SIGN and potently blocks dendritic cell mediated transfer of HIV-1 to CD4(+) T-lymphocytes. Virology 2009; 391:203-211.
59. + target cells from HIV infection but promotes the preferential transmission of R5 tropic HIV. J Immunol 2010; 185:7596-7604.
60. Keogan S, Wigdahl B, Krebs F: Human seminal fluid contains factors that modulate cervicovaginal epithelial monolayer integrity and may have roles in male-to-female transmission. 2012 International Microbicides Conference. Sydney, Australia, 2012.
61. Fox CA, Meldrum SJ, Watson BW: Continuous measurement by radio-telemetry of vaginal pH during human coitus. J Reprod Fertil 1973; 33:69-75.
62. Bouvet JP, Gresenguet G, Belec L: Vaginal pH neutralization by semen as a cofactor of HIV transmission. Clin Microbiol Infect 1997; 3:19-23.
63. Tevi-Benissan C, Belec L, Levy M, Schneider-Fauveau V, Si Mohamed A, Hallouin MC, Matta M, Grésenguet G: In vivo semen-associated pH neutralization of cervicovaginal secretions. Clin Diagn Lab Immunol 1997; 4:367-374.
64. Ongradi J, Ceccherini-Nelli L, Pistello M, Specter S, Bendinelli M: Acid sensitivity of cell-free and cell-associated HIV-1: clinical implications. AIDS Res Hum Retroviruses 1990; 6:1433-1436.
65. Lai SK, Hida K, Shukair S, Wang YY, Figueiredo A, Cone R, Hope TJ, Hanes J: Human immunodeficiency virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus. J Virol 2009; 83:11196-11200.
66. Aldunate M, Tyssen D, Johnson A, Zakir T, Sonza S, Moench T, Cone R, Tachedjian G: Vaginal concentrations of lactic acid potently inactivate HIV. J Antimicrob Chemother 2013; 68:2015-2025.
67. Kim KA, Yolamanova M, Zirafi O, Roan NR, Staendker L, Forssmann WG, Burgener A, Dejucq-Rainsford N, Hahn BH, Shaw GM, Greene WC, Kirchhoff F, Münch J: Semen-mediated enhancement of HIV infection is donor-dependent and correlates with the levels of SEVI. Retrovirology 2010; 7:55.
68. Munch J, Rucker E, Standker L, Adermann K, Goffinet C, Schindler M, Wildum S, Chinnadurai R, Rajan D, Specht A, Giménez-Gallego G, Sánchez PC, Fowler DM, Koulov A, Kelly JW, Mothes W, Grivel JC, Margolis L, Keppler OT, Forssmann WG, Kirchhoff F: Semen-derived amyloid fibrils drastically enhance HIV infection. Cell 2007; 131:1059-1071.
69. Roan NR, Munch J, Arhel N, Mothes W, Neidleman J, Kobayashi A, Smith-McCune K, Kirchhoff F, Greene WC: The cationic properties of SEVI underlie its ability to enhance human immunodeficiency virus infection. J Virol 2009; 83:73-80.
70. Roan NR, Muller JA, Liu H, Chu S, Arnold F, Stürzel CM, Walther P, Dong M, Witkowska HE, Kirchhoff F, Münch J, Greene WC: Peptides released by physiological cleavage of semen coagulum proteins form amyloids that enhance HIV infection. Cell Host Microbe 2011; 10:541-550.
71. Easterhoff D, Ontiveros F, Brooks LR, Kim Y, Ross B, Silva JN, Olsen JS, Feng C, Hardy DJ, Dunman PM, Dewhurst S: Semen-derived enhancer of viral infection (SEVI) binds bacteria, enhances bacterial phagocytosis by macrophages, and can protect against vaginal infection by a sexually transmitted bacterial pathogen. Antimicrob Agents Chemother 2013; 57:2443-2450.
72. Ceballos A, Remes Lenicov F, Sabatte J, Rodríguez Rodrígues C, Cabrini M, Jancic C, Raiden S, Donaldson M, Agustín Pasqualini R Jr, Marin-Briggiler C, Vazquez-Levin M, Capani F, Amigorena S, Geffner J: Spermatozoa capture HIV-1 through heparan sulfate and efficiently transmit the virus to dendritic cells. J Exp Med 2009; 206:2717-2733.
73. Bouhlal H, Chomont N, Haeffner-Cavaillon N, Kazatchkine MD, Belec L, Hocini H: Opsonization of HIV-1 by semen complement enhances infection of human epithelial cells. J Immunol 2002; 169:3301-3306.
74. Berlier W, Cremel M, Hamzeh H, Lévy R, Lucht F, Bourlet T, Pozzetto B, Delézay O: Seminal plasma promotes the attraction of Langerhans cells via the secretion of CCL20 by vaginal epithelial cells: involvement in the sexual transmission of HIV. Hum Reprod 2006; 21:1135-1142.
75. Kafka JK, Sheth PM, Nazli A, Osborne BJ, Kovacs C, Kaul R, Kaushic C: Endometrial epithelial cell response to semen from HIV-infected men during different stages of infection is distinct and can drive HIV-1-long terminal repeat. AIDS 2012; 26:27-36.
76. Anderson JA, Ping LH, Dibben O, Jabara CB, Arney L, Kincer L, Tang Y, Hobbs M, Hoffman I, Kazembe P, Jones CD, Borrow P, Fiscus S, Cohen MS, Swanstrom R: HIV-1 populations in semen arise through multiple mechanisms. PLoS Pathog 2010; 6:e1001053.
77. Miller CJ, Marthas M, Torten J, Alexander NJ, Moore JP, Doncel GF, Hendrickx AG: Intravaginal inoculation of rhesus macaques with cell-free simian immunodeficiency virus results in persistent or transient viremia 1. J Virol 1994; 68:6391-6400.
78. Neildez O, Le Grand R, Cheret A, Caufour P, Vaslin B, Matheux F, Théodoro F, Roques P, Dormont D: Variation in virological parameters and antibody responses in macaques after atraumatic vaginal exposure to a pathogenic primary isolate of SIVmac251. Res Virol 1998; 149:53-68.
79. Haase AT: Early events in sexual transmission of HIV and SIV and opportunities for interventions. Annu Rev Med 2011; 62:127-139.
80. Roberts L, Passmore JA, Mlisana K, Williamson C, Little F, Bebell LM, Walzl G, Abrahams MR, Woodman Z, Abdool Karim Q, Abdool Karim SS: Genital tract inflammation during early HIV-1 infection predicts higher plasma viral load set point in women. J Infect Dis 2012; 205:194-203.
81. Politch JA, Tucker L, Bowman FP, Anderson DJ: Concentrations and significance of cytokines and other immunologic factors in semen of healthy fertile men. Hum Reprod 2007; 22:2928-2935.
82. Lisco A, Munawwar A, Introini A, Vanpouille C, Saba E, Feng X, Grivel JC, Singh S, Margolis L: Semen of HIV-1-infected individuals: local shedding of herpesviruses and reprogrammed cytokine network. J Infect Dis 2012; 205:97-105.
83. Denison FC, Calder AA, Kelly RW: The action of prostaglandin E2 on the human cervix: stimulation of interleukin 8 and inhibition of secretory leukocyte protease inhibitor. Am J Obstet Gynecol 1999; 180:614-620.
84. Zalenskaya I: Manuscript in preparation. 2013.
85. Narimatsu R, Wolday D, Patterson BK: IL-8 increases transmission of HIV type 1 in cervical explant tissue 1. AIDS Res Hum Retroviruses 2005; 21:228-233.
86. + T cells are preferential targets for productive HIV type 1 infection regardless of their expression of integrin beta7. J Immunol 2011; 186:4618-4630.
87. Dieu-Nosjean MC, Massacrier C, Homey B, Vanbervliet B, Pin JJ, Vicari A, Lebecque S, Dezutter-Dambuyant C, Schmitt D, Zlotnik A, Caux C: Macrophage inflammatory protein 3alpha is expressed at inflamed epithelial surfaces and is the most potent chemokine known in attracting Langerhans cell precursors. J Exp Med 2000; 192:705-718.
88. Kawamura T, Kurtz SE, Blauvelt A, Shimada S: The role of Langerhans cells in the sexual transmission of HIV. J Dermatol Sci 2005; 40:147-155.
89. Lekkerkerker AN, van Kooyk Y, Geijtenbeek TB: Viral piracy: HIV-1 targets dendritic cells for transmission. Curr HIV Res 2006; 4:169-176.
90. 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.
91. Hirota K, Yoshitomi H, Hashimoto M, Maeda S, Teradaira S, Sugimoto N, Yamaguchi T, Nomura T, Ito H, Nakamura T, Sakaguchi N, Sakaguchi S: Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med 2007; 204:2803-2812.
92. Hirata T, Osuga Y, Takamura M, Kodama A, Hirota Y, Koga K, Yoshino O, Harada M, Takemura Y, Yano T, Taketani Y: Recruitment of CCR6-expressing Th17 cells by CCL 20 secreted from IL-1 beta-, TNF-alpha-, and IL-17A-stimulated endometriotic stromal cells. Endocrinology 2010; 151:5468-5476.
93. Miossec P: IL-17 and Th17 cells in human inflammatory diseases. Microbes Infect 2009; 11:625-630.
94. El Hed A, Khaitan A, Kozhaya L, Manel N, Daskalakis D, Borkowsky W, Valentine F, Littman DR, Unutmaz D: Susceptibility of human Th17 cells to human immunodeficiency virus and their perturbation during infection. J Infect Dis 2011; 201:843-854.
95. Kader M, Wang X, Piatak M, Lifson J, Roederer M, Veazey R, Mattapallil JJ: Alpha4(+)beta7(hi)CD4(+) memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection. Mucosal Immunol 2009; 2:439-449.
96. + T cell subset coexpressing multiple markers of HIV susceptibility. J Immunol 2011; 187:6032-6042.
97. + Th17 cells and gradual decline in regulatory T cells. AIDS 2010; 24:491-502.
98. Ghosh M, Shen Z, Schaefer TM, Fahey JV, Gupta P, Wira CR: CCL20/MIP3alpha is a novel anti-HIV-1 molecule of the human female reproductive tract. Am J Reprod Immunol 2009; 62:60-71.
99. Alexander NJ, Anderson DJ: Immunology of semen. Fertil Steril 1987; 47:192-205.
100. Robertson SA, Ingman WV, O'Leary S, Sharkey DJ, Tremellen KP: Transforming growth factor beta-a mediator of immune deviation in seminal plasma. J Reprod Immunol 2002; 57:109-128.
101. Lisco A, Introini A, Munawwar A, Vanpouille C, Grivel JC, Blank P, Singh S, Margolis L: HIV-1 imposes rigidity on blood and semen cytokine networks. Am J Reprod Immunol 2012; 68:515-521.
102. Maegawa M, Kamada M, Irahara M, Yamamoto S, Yoshikawa S, Kasai Y, Ohmoto Y, Gima H, Thaler CJ, Aono T: A repertoire of cytokines in human seminal plasma. J Reprod Immunol 2002; 54:33-42.
103. Carrette F, Surh CD: IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasis. Semin Immunol 2012; 24:209-217.
104. Park JH, Yu Q, Erman B, Appelbaum JS, Montoya-Durango D, Grimes HL, Singer A: Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survival. Immunity 2004; 21:289-302.
105. Beq S, Delfraissy JF, Theze J: Interleukin-7 (IL-7): immune function, involvement in the pathogenesis of HIV infection and therapeutic potential. Eur Cytokine Netw 2004; 15:279-289.
106. Crawley AM, Angel JB: The influence of HIV on CD127 expression and its potential implications for IL-7 therapy. Semin Immunol 2012; 24:231-240.
107. Introini A, Vanpouille C, Lisco A, Grivel JC, Margolis L: Interleukin-7 facilitates HIV-1 transmission to cervico-vaginal tissue ex vivo. PLoS Pathog 2013; 9:e1003148.
108. + T cells during the acute phase of SIV infection in rhesus macaques. PLoS Pathog 2012; 8:e1002636.
109. Wahl SM: Transforming growth factor-beta: innately bipolar. Curr Opin Immunol 2007; 19:55-62.
110. Kelly RW: Immunosuppressive mechanisms in semen: implications for contraception. Hum Reprod 1995; 10:1686-1693.
111. Sharkey DJ, Macpherson AM, Tremellen KP, Mottershead DG, Gilchrist RB, Robertson SA: TGF-beta mediates proinflammatory seminal fluid signaling in human cervical epithelial cells. J Immunol 2012; 189:1024-1035.
112. Lotz M, Seth P: TGF beta and HIV infection. Ann N Y Acad Sci 1993; 685:501-511.
113. Lazdins JK, Klimkait T, Alteri E, Walker M, Woods-Cook K, Cox D, Bilbe G, Shipman R, Cerletti N, McMaster G: TGF-beta: upregulator of HIV replication in macrophages. Res Virol 1991; 142:239-242.
114. Lazdins JK, Klimkait T, Woods-Cook K, Walker M, Alteri E, Cox D, Cerletti N, Shipman R, Bilbe G, McMaster G.: In vitro effect of transforming growth factor-beta on progression of HIV-1 infection in primary mononuclear phagocytes. J Immunol 1991; 147:1201-1207.
115. Poli G, Kinter AL, Justement JS, Bressler P, Kehrl JH, Fauci AS: Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage. J Exp Med 1991; 173:589-597.
116. Li JM, Shen X, Hu PP, Wang XF: Transforming growth factor beta stimulates the human immunodeficiency virus 1 enhancer and requires NF-kappaB activity. Mol Cell Biol 1998; 18:110-121.
117. Moriuchi M, Moriuchi H: Seminal fluid enhances replication of human T-cell leukemia virus type 1: implications for sexual transmission. J Virol 2004; 78:12709-12711.
118. Harizi H, Grosset C, Gualde N: Prostaglandin E2 modulates dendritic cell function via EP2 and EP4 receptor subtypes. J Leukoc Biol 2003; 73:756-763.
119. Kabashima K, Sakata D, Nagamachi M, Miyachi Y, Inaba K, Narumiya S: Prostaglandin E2-EP4 signaling initiates skin immune responses by promoting migration and maturation of Langerhans cells. Nat Med 2003; 9:744-749.
120. Tilley SL, Coffman TM, Koller BH: Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes. J Clin Invest 2001; 108:15-23.
121. Sakata D, Yao C, Narumiya S: Prostaglandin E2, an immunoactivator. J Pharmacol Sci 2010; 112:1-5.
122. Bankhurst AD: The modulation of human natural killer cell activity by prostaglandins. J Clin Lab Immunol 1982; 7:85-91.
123. Kalinski P: Regulation of immune responses by prostaglandin E2. J Immunol 2012; 188:21-28.
124. Templeton AA, Cooper I, Kelly RW: Prostaglandin concentrations in the semen of fertile men. J Reprod Fertil 1978; 52:147-150.
125. Sales KJ, Katz AA, Millar RP, Jabbour HN: Seminal plasma activates cyclooxygenase-2 and prostaglandin E2 receptor expression and signalling in cervical adenocarcinoma cells. Mol Hum Reprod 2002; 8:1065-1070.
126. Joseph T, Zalenskaya IA, Yousefieh N, Schriver SD, Cote LC, Chandra N, Doncel GF: Induction of cyclooxygenase (COX)-2 in human vaginal epithelial cells in response to TLR ligands and TNF-alpha. Am J Reprod Immunol 2012; 67:482-490.
127. Baba M: Recent status of HIV-1 gene expression inhibitors. Antiviral Res 2006; 71:301-306.