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

11 Citations (Scopus)

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

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Medroxyprogesterone Acetate
Endometrium
Cervix Uteri
HIV
Contraceptive Agents
HIV Receptors
Macrophages
T-Lymphocytes
Virus Activation
Luteal Phase
Vagina
Virus Diseases
Regulatory T-Lymphocytes
HIV-1
Interleukin-6
Cytokines
Injections

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Effects of depot-medroxyprogesterone acetate on the immune microenvironment of the human cervix and endometrium : Implications for HIV susceptibility. / Smith-McCune, K. K.; Hilton, J. F.; Shanmugasundaram, U.; Critchfield, J. W.; Greenblatt, R. M.; Seidman, D.; Averbach, S.; Giudice, L. C.; Shacklett, Barbara.

In: Mucosal Immunology, Vol. 10, No. 5, 01.09.2017, p. 1270-1278.

Research output: Contribution to journalArticle

Smith-McCune, KK, Hilton, JF, Shanmugasundaram, U, Critchfield, JW, Greenblatt, RM, Seidman, D, Averbach, S, Giudice, LC & Shacklett, B 2017, 'Effects of depot-medroxyprogesterone acetate on the immune microenvironment of the human cervix and endometrium: Implications for HIV susceptibility', Mucosal Immunology, vol. 10, no. 5, pp. 1270-1278. https://doi.org/10.1038/mi.2016.121
Smith-McCune, K. K. ; Hilton, J. F. ; Shanmugasundaram, U. ; Critchfield, J. W. ; Greenblatt, R. M. ; Seidman, D. ; Averbach, S. ; Giudice, L. C. ; Shacklett, Barbara. / Effects of depot-medroxyprogesterone acetate on the immune microenvironment of the human cervix and endometrium : Implications for HIV susceptibility. In: Mucosal Immunology. 2017 ; Vol. 10, No. 5. pp. 1270-1278.
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