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Estradiol Enhances CD4+ T-Cell Anti-Viral Immunity by Priming Vaginal DCs to Induce Th17 Responses via an IL-1-Dependent Pathway.
- Source :
- PLoS Pathogens; 5/5/2016, Vol. 12 Issue 5, p1-27, 27p
- Publication Year :
- 2016
-
Abstract
- Clinical and experimental studies have shown that estradiol (E2) confers protection against HIV and other sexually transmitted infections. Here, we investigated the underlying mechanism. Better protection in E2-treated mice, immunized against genital HSV-2, coincided with earlier recruitment and higher proportions of T<subscript>h</subscript>1 and T<subscript>h</subscript>17 effector cells in the vagina post-challenge, compared to placebo-treated controls. Vaginal APCs isolated from E2-treated mice induced 10-fold higher T<subscript>h</subscript>17 and T<subscript>h</subscript>1 responses, compared to APCs from progesterone-treated, placebo-treated, and estradiol-receptor knockout mice in APC-T cell co-cultures. CD11c<superscript>+</superscript> DCs in the vagina were the predominant APC population responsible for priming these T<subscript>h</subscript>17 responses, and a potent source of IL-6 and IL-1β, important factors for T<subscript>h</subscript>17 differentiation. T<subscript>h</subscript>17 responses were abrogated in APC-T cell co-cultures containing IL-1β KO, but not IL-6 KO vaginal DCs, showing that IL-1β is a critical factor for T<subscript>h</subscript>17 induction in the genital tract. E2 treatment in vivo directly induced high expression of IL-1β in vaginal DCs, and addition of IL-1β restored T<subscript>h</subscript>17 induction by IL-1β KO APCs in co-cultures. Finally, we examined the role of IL-17 in anti-HSV-2 memory T cell responses. IL-17 KO mice were more susceptible to intravaginal HSV-2 challenge, compared to WT controls, and vaginal DCs from these mice were defective at priming efficient T<subscript>h</subscript>1 responses in vitro, indicating that IL-17 is important for the generation of efficient anti-viral memory responses. We conclude that the genital mucosa has a unique microenvironment whereby E2 enhances CD4<superscript>+</superscript> T cell anti-viral immunity by priming vaginal DCs to induce T<subscript>h</subscript>17 responses through an IL-1-dependent pathway. [ABSTRACT FROM AUTHOR]
- Subjects :
- ESTRADIOL
CD4 antigen
ANTIVIRAL agents
INTERLEUKIN-1
PLACEBOS
Subjects
Details
- Language :
- English
- ISSN :
- 15537366
- Volume :
- 12
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- PLoS Pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 115151959
- Full Text :
- https://doi.org/10.1371/journal.ppat.1005589