Journal
MUCOSAL IMMUNOLOGY
Volume 10, Issue 5, Pages 1270-1278Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2016.121
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Funding
- NIH/NIAID P01 grant [AI083050]
- NIH/NIAID R01 grant [AI111925]
- National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI [UL1 TR000004]
- NCI [P30 CA093373]
- NIH/NCRR [C06 RR012088, S10 RR026825]
- James B. Pendleton Charitable Trust
- National Cancer Institute Cancer Center Support Grant [5P30 CA082103]
- US National Institutes of Health
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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+ Tcells 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.
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