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Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1

Version 2 2024-06-04, 04:16
Version 1 2015-02-17, 15:47
journal contribution
posted on 2024-06-04, 04:16 authored by A Meier, JJ Chang, ES Chan, RB Pollard, HK Sidhu, S Kulkarni, TF Wen, RJ Lindsay, Liliana OrellanaLiliana Orellana, D Mildvan, S Bazner, H Streeck, G Alter, JD Lifson, M Carrington, RJ Bosch, GK Robbins, M Altfeld
Manifestations of viral infections can differ between women and men, and marked sex differences have been described in the course of HIV-1 disease. HIV-1-infected women tend to have lower viral loads early in HIV-1 infection but progress faster to AIDS for a given viral load than men. Here we show substantial sex differences in the response of plasmacytoid dendritic cells (pDCs) to HIV-1. pDCs derived from women produce markedly more interferon-alpha (IFN-alpha) in response to HIV-1-encoded Toll-like receptor 7 (TLR7) ligands than pDCs derived from men, resulting in stronger secondary activation of CD8(+) T cells. In line with these in vitro studies, treatment-naive women chronically infected with HIV-1 had considerably higher levels of CD8(+) T cell activation than men after adjusting for viral load. These data show that sex differences in TLR-mediated activation of pDCs may account for higher immune activation in women compared to men at a given HIV-1 viral load and provide a mechanism by which the same level of viral replication might result in faster HIV-1 disease progression in women compared to men. Modulation of the TLR7 pathway in pDCs may therefore represent a new approach to reduce HIV-1-associated pathology.

History

Journal

Nature medicine

Volume

15

Pagination

955-959

Location

New York, NY

ISSN

1078-8956

eISSN

1546-170X

Language

eng

Publication classification

C Journal article, C1.1 Refereed article in a scholarly journal

Copyright notice

2008, Nature Publishing Group

Issue

8

Publisher

Nature Publishing Group