Host Defense Laboratory

• Defined mechanisms for progestin-induced impairment of innate and adaptive immunity. 
• Showed that estrogen both reverses progestin-mediated loss of the epithelial barrier and reduces mouse susceptibility to HIV and other genital pathogens.
• Synthesized a nonhormonal peptide product to enhance epithelial integrity and barrier function.
• Developing a microparticle-based vaccine platform to boost host immunity against intracellular microbial pathogens and tumors.

1. Liu M, Liao MJ, Fisher CJ, Vicetti Miguel RD, Cherpes TL. Methodology to streamline flow cytometric-based detection of early stage Plasmoidum parasitemia in mice. J Microbiol Methods 2022, 915: 106439.
2. Quispe Calla NE, Vicetti Miguel RD, Aceves KM, Cherpes TL. Ovariectomized mice and postmenopausal women exhibit analogous loss of genital epithelial integrity. Tissue Barriers 2021, 9(2); 1865760.
3. Vicetti Miguel RD, Quispe Calla NE, Cherpes TL. HIV, progestins, genital epithelial barrier function, and the burden of objectivity. Biol Reprod 2020, 103(2): 318-322.
4. Quispe Calla NE, Vicetti Miguel RD, Fritts L, Milles CJ, Aceves KM, Cherpes TL. Exogenous Sex Steroids Regulate Genital Epithelial Barrier Function in Female Rhesus Macaques. Biol Reprod 2020, 103(2): 310-317.
5. Quispe Calla NE, Vicetti Miguel RD, Torres AR, Trout W, Gabriel JM, Hatfield AM, Kwiek JJ, Kaur B, Thomas, Cherpes TL. Norethisterone enanthate increases mouse susceptibility to genital HSV-2 and HIV-1 infection. ImmunoHorizons 2020, 4(2): 72-81.
6. Vicetti Miguel RD, Quispe Calla NE, Aceves KM, Dueñas Lopez C, Cherpes TL. ECHO: context and limitations (letter to the editor). Lancet 2020, 395: e21.
7. Quispe Calla NE, Vicetti Miguel RD, Aceves KM, Torres A, Cherpes TL. Depot-medroxyprogesterone acetate reduces genital cell–cell adhesion molecule expression and increases genital herpes simplex virus type 2 infection susceptibility in a dose-dependent fashion. Contraception 2019, 100(5): 397-401.
8. Vicetti Miguel RD, Quispe Calla NE, Cherpes TL. Levonorgestrel and female genital tract immunity: time for a closer look. J Infect Dis 2018, 218(9): 1517-1518.
9. Quispe Calla NE, Vicetti Miguel RD, Glick M, Kwiek JJ, Gabriel J, Cherpes TL. Exogenous oestrogen inhibits genital transmission of cell-associated HIV-1 in DMPA-treated humanized mice. J Int AIDS Soc 2018, 21: e25063.
10. Vicetti Miguel RD, Quispe Calla NE, Dixon D, Foster RA, Gambotto A, Pavelko SD, Cherpes TL. IL-4-secreting eosinophils promote endometrial stromal cell proliferation and prevent Chlamydia-induced upper genital tract damage. Proc Natl Acad Sci USA 2017, 114(33): E6892-E6901.
11. Quispe Calla NE, Vicetti Miguel RD, Cherpes TL. Comment on 'Effects of injectable progestogen contraception versus the copper intrauterine device on HIV acquisition: sub-study of a pragmatic randomised controlled trial'. J Fam Plann Reprod Health Care 2017, 43(4): 342.
12. Vicetti Miguel RD, Quispe Calla NE, Cherpes TL. Setting sights on Chlamydia immunity's central paradigm: can we hit a moving target? Infect Immun 2017, 85(7): e00129-17.
13. Quispe Calla NE, Vicetti Miguel RD, Wayne Trout, Cherpes TL. Letter to the Editor: HIV and Hormonal Contraception: Bench and Bedside. J Acquir Immune Defic Syndr 2017, 74(3): e85-e86.
14. Quispe Calla NE, Vicetti Miguel RD, Mei A, Fan S, Cherpes TL. Dendritic cell function and pathogen-specific T cell immunity are inhibited in mice administered levonorgestrel prior to intranasal Chlamydia trachomatis infection. Sci Rep 2016, 6: 37723.
15. Quispe Calla NE, Vicetti Miguel RD, Prosper N Boyaka, Luanne Hall-Stoodley, Balveen Kaur, Wayne Trout, Pavelko SD, Cherpes TL. Medroxyprogesterone acetate and levonorgestrel increase genital mucosal permeability and enhance susceptibility to genital herpes simplex virus type 2 infection. Mucosal Immunol 2016, 9(6): 1571-1583.
16. Vicetti Miguel RD, Quispe Calla NE, Pavelko SD, Cherpes TL. Intravaginal Chlamydia trachomatis challenge infection elicits Th1 and Th17 immune responses in mice that promote pathogen clearance and genital tract damage. PLoS ONE 2016, 11(9): e0162445.
17. Vicetti Miguel RD, Henschel KJ, Quispe Calla NE, Cherpes TL. Fluorescent labeling reliably identifies Chlamydia trachomatis in living human endometrial cells and rapidly and accurately quantifies chlamydial inclusion forming units. J Microbiol Methods 2015, 119: 79-82.
18. Esber A, Vicetti Miguel RD, Cherpes TL, Klebanoff M, Gallo MF, Turner AN. Risk of bacterial vaginosis among women with herpes simplex virus type 2 infection: a systematic review and meta-analysis. J Infect Dis 2015, 212(1): 8-17.
19. Quispe Calla NE, Ghonime MG, Cherpes TL, Vicetti Miguel RD . Medroxyprogesterone acetate impairs human dendritic cell activation and function. Hum Reprod 2015, 30(5): 1169-1177.
20. Cherpes TL, Harvey SAK, Phillips JM, Vicetti Miguel RD, Melan MA, Quispe Calla NE & Hendricks RL. Use of transcriptional profiling to delineate the initial response of mice to intravaginal herpes simplex virus type 2 infection. Viral Immunol 2013, 26(3): 172-179.
21. Vicetti Miguel RD, Harvey S, LaFramboise WA, Reighard SD, Matthews DB & Cherpes TL. Human female genital tract infection by the obligate intracellular bacterium Chlamydia trachomatis elicits robust Type 2 immunity. PLoS ONE 2013, 8(3): e58565.
22. Pelvic Inflammatory Disease Workshop Proceedings Committee. Pelvic inflammatory disease: identifying research gaps--proceedings of a workshop sponsored by Department of Health and Human Services/National Institutes of Health/National Institute of Allergy and Infectious Diseases, November 3-4, 2011. Sex Transm Dis. 2013; 40(10):761-7.
23. Jeon S, St Leger AJ, Cherpes TL, Sheridan BS, Hendricks RL. PD-L1/B7-H1 regulates the survival but not the function of CD8+ T cells in herpes simplex virus type 1 latently infected trigeminal ganglia. J Immunol. 2013; 190(12): 6277-86.
24. Vicetti Miguel RD, Cherpes TL. Hypothesis: Chlamydia trachomatis infection of the female genital tract is controlled by Type 2 immunity. Med Hypotheses 2012, 79(6): 713-716.
25. Cherpes TL, Matthews DB, Maryak SA. Neonatal herpes simplex virus infection. Clin Obstet Gynecol. 2012; 55(4): 938-44.
26. Vicetti Miguel RD, Reighard SD, Chavez JM, Rabe LK, Maryak SA, Wiesenfeld HC & Cherpes TL. Transient detection of Chlamydial-specific Th1 memory cells in the peripheral circulation of women with history of Chlamydia trachomatis genital tract infection. Am J Repro Immunol 2012, 68(6): 499-506.
27. Vicetti Miguel RD, Maryak SA & Cherpes TL. Brefeldin A, but not monensin, enables flow cytometric detection of interleukin-4 in peripheral T cells responding to ex vivo stimulation with Chlamydia trachomatis. J Immunol Methods 2012, 384(1-2): 191-195.
28. Vicetti Miguel RD, Hendricks RL, Aguirre AJ, Melan MA, Terry-Allison T, Thomson AW & Cherpes TL. Dendritic cell activation and memory cell development are impaired among mice administered medroxyprogesterone acetate prior to mucosal herpes simplex virus type 1 infection. J Immunol 2012, 189(7): 3449-3461.
29. Ahmed A, Earl J, Retchless A, Hillier SL, Rabe LK, Cherpes TL, Powell E, Janto B, Eutsey R, Hiller NL, Boissy R, Dahlgren ME, Hall BG, Costerton JW, Post JC, Hu FZ, Ehrlich GD. Comparative genomic analyses of 17 clinical isolates of Gardnerella vaginalis provide evidence of multiple genetically isolated clades consistent with subspeciation into genovars. J Bacteriol. 2012; 194(15): 3922-37.
30. Stoner KA, Reighard SD, Vicetti Miguel RD, Landsittel D, Cosentino LA, Kant JA, Cherpes TL. Recalcitrance of bacterial vaginosis among herpes-simplex-virus-type-2-seropositive women. J Obstet Gynaecol Res 2011, 38(1): 77-83.
31. Cherpes TL, Rice PA, Sweet RL. Pelvic inflammatory disease. Infect Dis Obstet Gynecol. 2011; 2011: 714289.
32. Reighard SD, Sweet RL, Vicetti Miguel C., Vicetti Miguel RD, Chivukula M, Krishnamurti U & Cherpes TL. Endometrial leukocyte subpopulations associated with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis genital tract infections. Am J Ob Gyn 2011, 205(4): 324e1-7.
33. Vicetti Miguel RD, Chivukula M, Krishnamurti U, Amortegui AJ, Kant JA, Sweet RL, Wiesenfeld HC, Phillips JM & Cherpes TL. Limitations of criteria currently used to diagnose histologic endometritis. Path Res Pract 2011, 207(11): 680-685.
34. Chavez JM, Vicetti Miguel RD, Cherpes TL. Chlamydia trachomatis infection control programs: lessons learned and implications for vaccine development. Infect Dis Obstet Gynecol 2011, 2011: 754060.
35. McKenna KC, Vicetti Miguel RD, Beatty KM, Bilonick RA. A caveat for T cell transfer studies: generation of cytotoxic anti-Thy1.2 antibodies in Thy1.1 congenic mice given Thy1.2+ tumors or T cells. J Leukoc Biol. 2011 Feb;89(2):291-300.
36. Vicetti Miguel RD, Cherpes TL, Watson LJ, McKenna KC. CTL induction of tumoricidal nitric oxide production by intratumoral macrophages is critical for tumor elimination. J Immunol 2010, 185(11): 6706-18.
37. Vicetti Miguel RD, Sheridan BS, Harvey SA, Schreiner RS, Hendricks RL & Cherpes TL. 17-beta estradiol promotion of herpes simplex virus type 1 reactivation is estrogen receptor dependent. J Virol 2010, 84(1): 565-572.
38. Frank GM, Lepisto AJ, Freeman ML, Sheridan BS, Cherpes TL, Hendricks RL. Early CD4(+) T cell help prevents partial CD8(+) T cell exhaustion and promotes maintenance of Herpes Simplex Virus 1 latency. J Immunol. 2010; 184(1): 277-86.
39. Sheridan BS, Cherpes TL, Urban J, Kalinski P, Hendricks RL. Reevaluating the CD8 T-cell response to herpes simplex virus type 1: involvement of CD8 T cells reactive to subdominant epitopes. J Virol. 2009; 83(5): 2237-45.
40. Leyland B, Kennedy MR, Wimberly YH, Levine BJ, Cherpes TL. Serologic detection of herpes simplex virus type 2 antibodies among pregnant women using a point-of-care test from Focus Diagnostics. J Clin Virol. 2009; 44(2): 125-8.
41. Cherpes TL, Busch JL, Sheridan BS, Harvey SA, Hendricks RL. Medroxyprogesterone acetate inhibits CD8+ T cell viral-specific effector function and induces herpes simplex virus type 1 reactivation. J Immunol. 2008; 181(2): 969-75.
42. Cherpes TL, Marrazzo JM, Cosentino LA, Meyn LA, Murray PJ, Hillier SL. Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis. Sex Transm Infect. 2008; 84(1): 57-61.
43. Cherpes TL, Hillier SL, Meyn LA, Busch JL, Krohn MA. A delicate balance: risk factors for acquisition of bacterial vaginosis include sexual activity, absence of hydrogen peroxide-producing lactobacilli, black race, and positive herpes simplex virus type 2 serology. Sex Transm Dis. 2008; 35(1): 78-83.
44. Cherpes TL, Wiesenfeld HC, Melan MA, Kant JA, Cosentino LA, Meyn LA, Hillier SL. The associations between pelvic inflammatory disease, Trichomonas vaginalis infection, and positive herpes simplex virus type 2 serology. Sex Transm Dis. 2006; 33(12): 747-52.
45. Divito S, Cherpes TL, Hendricks RL. A triple entente: virus, neurons, and CD8+ T cells maintain HSV-1 latency. Immunol Res. 2006; 36(1-3): 119-26.
46. Cherpes TL, Melan MA, Kant JA, Cosentino LA, Meyn LA, Hillier SL. Genital tract shedding of herpes simplex virus type 2 in women: effects of hormonal contraception, bacterial vaginosis, and vaginal group B Streptococcus colonization. Clin Infect Dis. 2005; 40(10): 1422-8.
47. Cherpes TL, Meyn LA, Hillier SL. Cunnilingus and vaginal intercourse are risk factors for herpes simplex virus type 1 acquisition in women. Sex Transm Dis. 2005; 32(2): 84-9.
48. Cherpes TL, Meyn LA, Krohn MA, Lurie JG, Hillier SL. Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Clin Infect Dis. 2003; 37(3): 319-25.
49. Cherpes TL, Meyn LA, Hillier SL. Plasma versus serum for detection of herpes simplex virus type 2-specific immunoglobulin G antibodies with a glycoprotein G2-based enzyme immunoassay. J Clin Microbiol. 2003; 41(6): 2758-9.
50. Cherpes TL, Meyn LA, Krohn MA, Hillier SL. Risk factors for infection with herpes simplex virus type 2: role of smoking, douching, uncircumcised males, and vaginal flora. Sex Transm Dis. 2003; 30(5): 405-10.
51. Cherpes TL, Ashley RL, Meyn LA, Hillier SL. Longitudinal reliability of focus glycoprotein G-based type-specific enzyme immunoassays for detection of herpes simplex virus types 1 and 2 in women. J Clin Microbiol. 2003; 41(2): 671-4.
52. Cherpes TL, Kusne S, Hillier SL. Haemophilus influenzae septic abortion. Infect Dis Obstet Gynecol. 2002; 10(3): 161-4.
53. Fernihough JK, Richmond RS, Carlson CS, Cherpes T, Holly JM, Loeser RF. Estrogen replacement therapy modulation of the insulin-like growth factor system in monkey knee joints. Arthritis Rheum. 1999; 42(10): 2103-11.

Project title: Estrogen reverses progestin-mediated loss of genital mucosal barrier function

Funding: Eunice Kennedy Shriver National Institute of Child Health and Human Development

Objective: Define sex steroid-mediated effects on epithelial integrity and function