Uterine Epithelial Cell Regulation of DC-SIGN Expression Inhibits Transmitted/founder HIV-1 Trans Infection by Immature Dendritic Cells

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2010 Dec 24

PMID 21179465

Citations 28

Authors

Daniel O Ochiel

Christina Ochsenbauer

John C Kappes

Mimi Ghosh

John V Fahey

Charles R Wira

Affiliations

Soon will be listed here.

Abstract

Background: Sexual transmission accounts for the majority of HIV-1 infections. In over 75% of cases, infection is initiated by a single variant (transmitted/founder virus). However, the determinants of virus selection during transmission are unknown. Host cell-cell interactions in the mucosa may be critical in regulating susceptibility to infection. We hypothesized in this study that specific immune modulators secreted by uterine epithelial cells modulate susceptibility of dendritic cells (DC) to infection with HIV-1.

Methodology/principal Findings: Here we report that uterine epithelial cell secretions (i.e. conditioned medium, CM) decreased DC-SIGN expression on immature dendritic cells via a transforming growth factor beta (TGF-β) mechanism. Further, CM inhibited dendritic cell-mediated trans infection of HIV-1 expressing envelope proteins of prototypic reference. Similarly, CM inhibited trans infection of HIV-1 constructs expressing envelopes of transmitted/founder viruses, variants that are selected during sexual transmission. In contrast, whereas recombinant TGF- β1 inhibited trans infection of prototypic reference HIV-1 by dendritic cells, TGF-β1 had a minimal effect on trans infection of transmitted/founder variants irrespective of the reporter system used to measure trans infection.

Conclusions/significance: Our results provide the first direct evidence for uterine epithelial cell regulation of dendritic cell transmission of infection with reference and transmitted/founder HIV-1 variants. These findings have immediate implications for designing strategies to prevent sexual transmission of HIV-1.

Citing Articles

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The Roles of Skin Langerhans Cells in Immune Tolerance and Cancer Immunity.

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"Iron triangle" of regulating the uterine microecology: Endometrial microbiota, immunity and endometrium.

Zhu N, Yang X, Liu Q, Chen Y, Wang X, Li H Front Immunol. 2022; 13:928475.

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Development of a Novel Primary Human Monocyte-Derived Macrophage Model To Study Reactivation of HIV-1 Transcription.

Wong M, Johnson C, Hearps A, Jaworowski A J Virol. 2021; 95(19):e0022721.

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Direct and Indirect endocrine-mediated suppression of human endometrial CD8+T cell cytotoxicity.

Shen Z, Rodriguez-Garcia M, Patel M, Wira C Sci Rep. 2021; 11(1):1773.

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