Effects of depot-medroxyprogesterone acetate on the immune microenvironment of the human cervix and endometrium: Implications for HIV susceptibility

K. K. Smith-McCune, J. F. Hilton, U. Shanmugasundaram, J. W. Critchfield, R. M. Greenblatt, D. Seidman, S. Averbach, L. C. Giudice, Barbara Shacklett

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Depot-medroxyprogesterone acetate is a commonly used injectable contraceptive that has been associated with an increased risk of HIV acquisition. This study compares effects of depot-medroxyprogesterone acetate on immune parameters from several upper reproductive tract compartments relevant to HIV-1 susceptibility in repetitive samples from 15 depot-medroxyprogesterone acetate users and 27 women not on hormonal contraceptives. Compared with samples from unexposed women in the mid-luteal phase, depot-medroxyprogesterone acetate use was associated with: increased endocervical concentrations of MCP1 and IFNalpha2; decreased endocervical concentrations of IL1beta and IL6; increased proportions of endometrial CD4+ and CD8+ cells expressing the activation marker HLADR; increased density of endometrial macrophages; and decreased density of endometrial regulatory T cells. Unlike previous reports with samples from the vagina, we did not observe increased expression of the HIV co-receptor CCR5 on CD4+ T cells in the endocervix or endometrium. Our results indicate important differences in anatomic compartments regarding mechanisms by which depot-medroxyprogesterone acetate could be associated with increased risk of HIV acquisition, including increased recruitment of macrophages to the endometrium, decreased levels of pro-inflammatory cytokines in the endocervix possibly leading to enhanced susceptibility to viral infection, and activation of endometrial T cells.

Original languageEnglish (US)
Pages (from-to)1270-1278
Number of pages9
JournalMucosal Immunology
Volume10
Issue number5
DOIs
StatePublished - Sep 1 2017

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Smith-McCune, K. K., Hilton, J. F., Shanmugasundaram, U., Critchfield, J. W., Greenblatt, R. M., Seidman, D., Averbach, S., Giudice, L. C., & Shacklett, B. (2017). Effects of depot-medroxyprogesterone acetate on the immune microenvironment of the human cervix and endometrium: Implications for HIV susceptibility. Mucosal Immunology, 10(5), 1270-1278. https://doi.org/10.1038/mi.2016.121