New Approaches to Making the Microenvironment of the Female Reproductive Tract Hostile to HIV

American Journal of Reproductive Immunology

Volumn 65, Issue 3, 2011, Pages 334-343

  Fahey, John V ^a   Bodwell, Jack E ^a   Hickey, Danica K ^a   Ghosh, Mimi ^a   Muia, Maria N ^a   Wira, Charles R ^a  

^a DARTMOUTH MEDICAL SCHOOL   (United States)

Author keywords

Antimicrobials; Female reproductive tract; HIV; Selective estrogen response modifier

Indexed keywords

ANTIINFECTIVE AGENT; CATHEPSIN B; CATHEPSIN D; CATHEPSIN G; ELAFIN; ESTRADIOL; ESTROGEN; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; MACROPHAGE INFLAMMATORY PROTEIN 3ALPHA; RANTES; SECRETORY LEUKOCYTE PROTEINASE INHIBITOR;

ENDOCRINOLOGY; FEMALE GENITAL SYSTEM; HORMONAL REGULATION; HORMONE RELEASE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INNATE IMMUNITY; LACTOBACILLUS; MENSTRUAL CYCLE; MICROENVIRONMENT; NONHUMAN; PRIORITY JOURNAL; REVIEW;

ANTI-HIV AGENTS; BACTERIAL PHYSIOLOGICAL PHENOMENA; ELAFIN; ESTRADIOL; FEMALE; GENITALIA, FEMALE; HIV INFECTIONS; HUMANS; IMMUNITY, INNATE; IMMUNITY, MUCOSAL; LACTOBACILLUS; MUCOUS MEMBRANE; SELECTIVE ESTROGEN RECEPTOR MODULATORS;

EID: 79551617335     PISSN: 10467408     EISSN: 16000897     Source Type: Journal    
DOI: 10.1111/j.1600-0897.2010.00949.x     Document Type: Review

References (85)

1. 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.
2. Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D: Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 2010; 329:1168-1174.
3. Ghosh M, Fahey J, Wira C: Differential susceptibility of HIV strains to innate immune factors in human cervical-vaginal secretions. Virus Adapt Treat 2010; 2010:63-71.
4. Wira CR, Fahey JV, Ghosh M, Patel MV, Hickey DK, Ochiel DO: Sex hormone regulation of innate immunity in the female reproductive tract: the role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens. Am J Reprod Immunol 2010; 63:544-565.
5. 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.
6. Connor RI: Sensitivity of non-clade B primary HIV-1 isolates to mildly acidic pH. J Acquir Immune Defic Syndr 2006; 43:499-501.
7. Fletcher PS, Harman SJ, Boothe AR, Doncel GF, Shattock RJ: Preclinical evaluation of lime juice as a topical microbicide candidate. Retrovirology 2008; 5:3.
8. Baeten JM, Hassan WM, Chohan V, Richardson BA, Mandaliya K, Ndinya-Achola JO, Jaoko W, McClelland RS: Prospective study of correlates of vaginal Lactobacillus colonisation among high-risk HIV-1 seronegative women. Sex Transm Infect 2009; 85:348-353.
9. Witkin SS, Linhares IM, Giraldo P: Bacterial flora of the female genital tract: function and immune regulation. Best Pract Res Clin Obstet Gynaecol 2007; 21:347-354.
10. O'Hanlon DE, Lanier BR, Moench TR, Cone RA: Cervicovaginal fluid and semen block the microbicidal activity of hydrogen peroxide produced by vaginal lactobacilli. BMC Infect Dis 2010; 10:1-8.
11. 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.
12. Wira CR, Ghosh M, Smith JM, Shen L, Connor RI, Sundstrom P, Frechette GM, Hill EM, Fahey JV: Epithelial Cell Secretions from the Human Female Reproductive Tract Inhibit Sexually Transmitted Pathogens and Candida albicans but not Lactobacillus. Mucosal Immunol 2010; In Press.
13. Secchi M, Xu Q, Lusso P, Vangelista L: The superior folding of a RANTES analogue expressed in lactobacilli as compared to mammalian cells reveals a promising system to screen new RANTES mutants. Protein Expr Purif 2009; 68:34-41.
14. Chang TL, Chang CH, Simpson DA, Xu Q, Martin PK, Lagenaur LA, Schoolnik GK, Ho DD, Hillier SL, Holodniy M, Lewicki JA, Lee PP: Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4. Proc Natl Acad Sci U S A 2003; 100:11672-11677.
15. Czaja CA, Stapleton AE, Yarova-Yarovaya Y, Stamm WE: Phase I trial of a Lactobacillus crispatus vaginal suppository for prevention of recurrent urinary tract infection in women. Infect Dis Obstet Gynecol 2007; 2007:35387.
16. Ghosh M, Shen Z, Fahey JV, Cu-Uvin S, Mayer K, Wira CR: Trappin-2/Elafin: a novel innate anti-human immunodeficiency virus-1 molecule of the human female reproductive tract. Immunology 2009; 129:207-219.
17. Iqbal SM, Ball TB, Levinson P, Maranan L, Jaoko W, Wachihi C, Pak BJ, Podust VN, Broliden K, Hirbod T, Kaul R, Plummer FA: Elevated elafin/trappin-2 in the female genital tract is associated with protection against HIV acquisition. AIDS 2009; 23:1669-1677.
18. Bingle CD, Vyakarnam A: Novel innate immune functions of the whey acidic protein family. Trends Immunol 2008; 29:444-453.
19. Bauer F, Schweimer K, Kluver E, Conejo-Garcia JR, Forssmann WG, Rosch P, Adermann K, Sticht H: Structure determination of human and murine beta-defensins reveals structural conservation in the absence of significant sequence similarity. Protein Sci 2001; 10:2470-2479.
20. Pusch O, Boden D, Hannify S, Lee F, Tucker LD, Boyd MR, Wells JM, Ramratnam B: Bioengineering lactic acid bacteria to secrete the HIV-1 virucide cyanovirin. J Acquir Immune Defic Syndr 2005; 40:512-520.
21. Pusch O, Kalyanaraman R, Tucker LD, Wells JM, Ramratnam B, Boden D: An anti-HIV microbicide engineered in commensal bacteria: secretion of HIV-1 fusion inhibitors by lactobacilli. AIDS 2006; 20:1917-1922.
22. Kian Tee M, Rogatsky I, Tzagarakis-Foster C, Cvoro A, An J, Christy RJ, Yamamoto KR, Leitman DC: Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Mol Biol Cell 2004; 15:1262-1272.
23. Matsuzaki S, Fukaya T, Suzuki T, Murakami T, Sasano H, Yajima A: Oestrogen receptor alpha and beta mRNA expression in human endometrium throughout the menstrual cycle. Mol Hum Reprod 1999; 5:559-564.
24. Dutertre M, Smith CL: Molecular mechanisms of selective estrogen receptor modulator (SERM) action. J Pharmacol Exp Ther 2000; 295:431-437.
25. Wakeling AE, Valcaccia B, Newboult E, Green LR: Non-steroidal antioestrogens - receptor binding and biological response in rat uterus, rat mammary carcinoma and human breast cancer cells. J Steroid Biochem 1984; 20:111-120.
26. Weatherman RV, Clegg NJ, Scanlan TS: Differential SERM activation of the estrogen receptors (ERalpha and ERbeta) at AP-1 sites. Chem Biol 2001; 8:427-436.
27. de Cupis A, Noonan D, Pirani P, Ferrera A, Clerico L, Favoni RE: Comparison between novel steroid-like and conventional nonsteroidal antioestrogens in inhibiting oestradiol- and IGF-I-induced proliferation of human breast cancer-derived cells. Br J Pharmacol 1995; 116:2391-2400.
28. Wakeling AE, Dukes M, Bowler J: A potent specific pure antiestrogen with clinical potential. Cancer Res 1991; 51:3867-3873.
29. Compton DR, Sheng S, Carlson KE, Rebacz NA, Lee IY, Katzenellenbogen BS, Katzenellenbogen JA: Pyrazolo[1, 5-a]pyrimidines: estrogen receptor ligands possessing estrogen receptor beta antagonist activity. J Med Chem 2004; 47:5872-5893.
30. Ning M, Zhou C, Weng J, Zhang S, Chen D, Yang C, Wang H, Ren J, Zhou L, Jin C, Wang M-W: Biological activities of a novel selective oestrogen receptor modulator derived from raloxifene (Y134). Br J Pharmacol 2007; 150:19-28.
31. Nazli A, Chan O, Dobson-Belaire WN, Ouellet M, Tremblay MJ, Gray-Owen SD, Arsenault AL, Kaushic C: Exposure to HIV-1 directly impairs mucosal epithelial barrier integrity allowing microbial translocation. PLoS Pathog 2010; 6:e1000852.
32. 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.
33. Cooke PS, Buchanan DL, Young P, Setiawan T, Brody J, Korach KS, Taylor J, Lubahn DB, Cunha GR: Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium. Proc Natl Acad Sci U S A 1997; 94:6535-6540.
34. Coleman KD, Wright JA, Ghosh M, Wira CR, Fahey JV: Estradiol modulation of hepatocyte growth factor by stromal fibroblasts in the female reproductive tract. Fertil Steril 2009; 92:1107-1109.
35. Haddad SN, Wira CR: Keratinocyte Growth Factor Stimulates Macrophage Inflammatory Protein 3alpha and Keratinocyte-derived Chemokine Secretion by Mouse Uterine Epithelial Cells. Am J Reprod Immunol 2010; 64:197-211.
36. Cooke PS, Buchanan DL, Lubahn DB, Cunha GR: Mechanism of estrogen action: lessons from the estrogen receptor-alpha knockout mouse. Biol Reprod 1998; 59:470-475.
37. Hall JM, Couse JF, Korach KS: The multifaceted mechanisms of estradiol and estrogen receptor signaling. J Biol Chem 2001; 276:36869-36872.
38. Guyot N, Zani ML, Berger P, Dallet-Choisy S, Moreau T: Proteolytic susceptibility of the serine protease inhibitor trappin-2 (pre-elafin): evidence for tryptase-mediated generation of elafin. Biol Chem 2005; 386:391-399.
39. Jokimaa V, Oksjoki S, Kujari H, Vuorio E, Anttila L: Expression patterns of cathepsins B, H, K, L and S in the human endometrium. Mol Hum Reprod 2001; 7:73-78.
40. McQuibban GA, Gong JH, Tam EM, McCulloch CA, Clark-Lewis I, Overall CM: Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3. Science 2000; 289:1202-1206.
41. Wilson CL, Ouellette AJ, Satchell DP, Ayabe T, Lopez-Boado YS, Stratman JL, Hultgren SJ, Matrisian LM, Parks WC: Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense. Science 1999; 286:113-117.
42. Zhang K, McQuibban GA, Silva C, Butler GS, Johnston JB, Holden J, Clark-Lewis I, Overall CM, Power C: HIV-induced metalloproteinase processing of the chemokine stromal cell derived factor-1 causes neurodegeneration. Nat Neurosci 2003; 6:1064-1071.
43. Hasan L, Mazzucchelli L, Liebi M, Lis M, Hunger RE, Tester A, Overall CM, Wolf M: Function of liver activation-regulated chemokine/CC chemokine ligand 20 is differently affected by cathepsin B and cathepsin D processing. J Immunol 2006; 176:6512-6522.
44. Lim JK, Lu W, Hartley O, DeVico AL: N-terminal proteolytic processing by cathepsin G converts RANTES/CCL5 and related analogs into a truncated 4-68 variant. J Leukoc Biol 2006; 80:1395-1404.
45. Taggart CC, Greene CM, Smith SG, Levine RL, McCray PB Jr, O'Neill S, McElvaney NG: Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. J Immunol 2003; 171:931-937.
46. Cummins JE, Christensen L, Lennox JL, Bush TJ, Wu Z, Malamud D, Evans-Strickfaden T, Siddig A, Caliendo AM, Hart CE, Dezzutti CS: Mucosal innate immune factors in the female genital tract are associated with vaginal HIV-1 shedding independent of plasma viral load. AIDS Res Hum Retroviruses 2006; 22:788-795.
47. El Messaoudi K, Thiry L, Van Tieghem N, Liesnard C, Englert Y, Moguilevsky N, Bollen A: HIV-1 infectivity and host range modification by cathepsin D present in human vaginal secretions. AIDS 1999; 13:333-339.
48. El Messaoudi K, Thiry LF, Liesnard C, Van Tieghem N, Bollen A, Moguilevsky N: A human milk factor susceptible to cathepsin D inhibitors enhances human immunodeficiency virus type 1 infectivity and allows virus entry into a mammary epithelial cell line. J Virol 2000; 74:1004-1007.
49. Shaw JL, Diamandis EP: Regulation of human tissue kallikrein-related peptidase expression by steroid hormones in 32 cell lines. Biol Chem 2008; 389:1409-1419.
50. Shaw JL, Diamandis EP: A potential role for tissue kallikrein-related peptidases in human cervico-vaginal physiology. Biol Chem 2008; 389:681-688.
51. Steinstraesser L, Tippler B, Mertens J, Lamme E, Homann HH, Lehnhardt M, Wildner O, Steinau HU, Uberla K: Inhibition of early steps in the lentiviral replication cycle by cathelicidin host defense peptides. Retrovirology 2005; 2:2.
52. Yamasaki K, Schauber J, Coda A, Lin H, Dorschner RA, Schechter NM, Bonnart C, Descargues P, Hovnanian A, Gallo RL: Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin. FASEB J 2006; 20:2068-2080.
53. Burgener A, Boutilier J, Wachihi C, Kimani J, Carpenter M, Westmacott G, Cheng K, Ball TB, Plummer F: Identification of differentially expressed proteins in the cervical mucosa of HIV-1-resistant sex workers. J Proteome Res 2008; 7:4446-4454.
54. Moriuchi H, Moriuchi M, Fauci AS: Cathepsin G, a neutrophil-derived serine protease, increases susceptibility of macrophages to acute human immunodeficiency virus type 1 infection. J Virol 2000; 74:6849-6855.
55. Shaw JL, Smith CR, Diamandis EP: Proteomic analysis of human cervico-vaginal fluid. J Proteome Res 2007; 6:2859-2865.
56. Singh PK, Tack BF, McCray PB Jr, Welsh MJ: Synergistic and additive killing by antimicrobial factors found in human airway surface liquid. Am J Physiol Lung Cell Mol Physiol 2000; 279:L799-L805.
57. 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.
58. Turpin JA, Schaeffer CA, Bu M, Graham L, Buckheit RW Jr, Clanton D, Rice WG: Human immunodeficiency virus type-1 (HIV-1) replication is unaffected by human secretory leukocyte protease inhibitor. Antiviral Res 1996; 29:269-277.
59. Konopka K, Shine N, Pretzer E, Duzgunes N: Secretory leukocyte protease inhibitor (SLPI): oxidation of SLPI does not explain its variable anti-HIV activity. J Dent Res 1999; 78:1773-1776.
60. Shine NR, Wang SC, Konopka K, Burks EA, Duzgunes N, Whitman CP: Secretory leukocyte protease inhibitor: inhibition of human immunodeficiency virus-1 infection of monocytic THP-1 cells by a newly cloned protein. Bioorg Chem 2002; 30:249-263.
61. Pelletier G, El-Alfy M: Immunocytochemical localization of estrogen receptors alpha and beta in the human reproductive organs. J Clin Endocrinol Metab 2000; 85:4835-4840.
62. Taylor A, Al-Azzawi F: Immunolocalisation of oestrogen receptor beta in human tissues. J Mol Endocrinol 2000; 24:145-155.
63. Iwai T, Nanbu Y, Iwai M, Taii S, Fujii S, Mori T: Immunohistochemical localization of oestrogen receptors and progesterone receptors in the human ovary throughout the menstrual cycle. Virchows Arch A Pathol Anat Histopathol 1990; 417:369-375.
64. Maybin JA, Duncan WC: The human corpus luteum: which cells have progesterone receptors? Reproduction 2004; 128:423-431.
65. Pelletier G, Labrie C, Labrie F: Localization of oestrogen receptor alpha, oestrogen receptor beta and androgen receptors in the rat reproductive organs. J Endocrinol 2000; 165:359-370.
66. Enmark E, Pelto-Huikko M, Grandien K, Lagercrantz S, Lagercrantz J, Fried G, Nordenskjöld M, Gustafsson JA: Human estrogen receptor beta-gene structure, chromosomal localization, and expression pattern. J Clin Endocrinol Metab 1997; 82:4258-4265.
67. Ulziibat S, Ejima K, Shibata Y, Hishikawa Y, Kitajima M, Fujishita A, Ishimaru T, Koji T: Identification of estrogen receptor beta-positive intraepithelial lymphocytes and their possible roles in normal and tubal pregnancy oviducts. Hum Reprod 2006; 21:2281-2289.
68. Cretoiu SM, Cretoiu D, Suciu L, Popescu LM: Interstitial Cajal-like cells of human Fallopian tube express estrogen and progesterone receptors. J Mol Hist 2009; 40:387-394.
69. Jones RK, Bulmer JN, Searle RF: Immunohistochemical characterization of proliferation, oestrogen receptor and progesterone receptor expression in endometriosis: comparison of eutopic and ectopic endometrium with normal cycling endometrium. Hum Reprod 1995; 10:3272-3279.
70. Lecce G, Meduri G, Ancelin M, Bergeron C, Perrot-Applanat M: Presence of estrogen receptor beta in the human endometrium through the cycle: expression in glandular, stromal, and vascular cells. J Clin Endocrinol Metab 2001; 86:1379-1386.
71. Mylonas I, Jeschke U, Shabani N, Kuhn C, Balle A, Kriegel S, Kupka MS, Friese K: Immunohistochemical analysis of estrogen receptor alpha, estrogen receptor beta and progesterone receptor in normal human endometrium. Acta Histochem 2004; 106:245-252.
72. Remoue F, Jacobs N, Miot V, Boniver J, Delvenne P: High intraepithelial expression of estrogen and progesterone receptors in the transformation zone of the uterine cervix. Am J Obstet Gynecol 2003; 189:1660-1665.
73. Fu X, Blaydes BS, Weis CC, Latendresse JR, Muskhelishvili L, Sutter TR, Delclos KB: Effects of dietary soy and estrous cycle on adrenal cytochrome p450 1B1 expression and DMBA metabolism in adrenal glands and livers in female Sprague-Dawley rats. Chem Biol Interact 2003; 146:273-284.
74. Hodgins MB, Spike RC, Mackie RM, MacLean AB: An immunohistochemical study of androgen, oestrogen and progesterone receptors in the vulva and vagina. Br J Obstet Gynaecol 1998; 105:216-222.
75. Murphy AJ, Guyre PM, Wira CR, Pioli PA: Estradiol regulates expression of estrogen receptor ERalpha46 in human macrophages. PLoS ONE 2009; 4:e5539.
76. Phiel KL, Henderson RA, Adelman SJ, Elloso MM: Differential estrogen receptor gene expression in human peripheral blood mononuclear cell populations. Immunol Lett 2005; 97:107-113.
77. Schust DJ, Anderson DJ, Hill JA: Progesterone-induced immunosuppression is not mediated through the progesterone receptor. Hum Reprod 1996; 11:980-985.
78. Khan KN, Masuzaki H, Fujishita A, Kitajima M, Sekine I, Matsuyama T, Ishimaru T: Estrogen and progesterone receptor expression in macrophages and regulation of hepatocyte growth factor by ovarian steroids in women with endometriosis. Hum Reprod 2005; 20:2004-2013.
79. Komi J, Lassila O: Nonsteroidal anti-estrogens inhibit the functional differentiation of human monocyte-derived dendritic cells. Blood 2000; 95:2875-2882.
80. Sapino A, Cassoni P, Ferrero E, Bongiovanni M, Righi L, Fortunati N, Crafa P, Chiarle R, Bussolati G: Estrogen receptor alpha is a novel marker expressed by follicular dendritic cells in lymph nodes and tumor-associated lymphoid infiltrates. Am J Pathol 2003; 163:1313-1320.
81. Aerts J, Wetzels Y, Cohen N, Aerssens J: Data mining of public SNP databases for the selection of intragenic SNPs. Hum Mutat 2002; 20:162-173.
82. Molero L, García-Durán M, Diaz-Recasens J, Rico L, Casado S, López-Farré A: Expression of estrogen receptor subtypes and neuronal nitric oxide synthase in neutrophils from women and men: regulation by estrogen. Cardiovasc Res 2002; 56:43-51.
83. Arruvito L, Giulianelli S, Flores AC, Paladino N, Barboza M, Lanari C, Fainboim L: NK cells expressing a progesterone receptor are susceptible to progesterone-induced apoptosis. J Immunol 2008; 180:5746-5753.
84. Henderson TA, Saunders PTK, Moffett-King A, Groome NP, Critchley HOD: Steroid receptor expression in uterine natural killer cells. J Clin Endocrinol Metab 2003; 88:440-449.
85. Szekeres-Bartho J, Szekeres G, Debre P, Autran B, Chaouat G: Reactivity of lymphocytes to a progesterone receptor-specific monoclonal antibody. Cell Immunol 1990; 125:273-283.