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Sex Differences in Primary HIV Infection: Revisiting the Role of TLR7-Driven Type 1 IFN Production by Plasmacytoid Dendritic Cells in Women

Plasmacytoid dendritic cells (pDCs) produce type I interferon (IFN-I) during HIV-1 infection in response to TLR7 stimulation. However, IFN-I-signaling has been shown to play opposite effects in HIV-1 and SIV infection. TLR7-driven type I interferon production in pDCs is higher in women than in men d...

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Autor principal: Guéry, Jean-Charles
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432934/
https://www.ncbi.nlm.nih.gov/pubmed/34512664
http://dx.doi.org/10.3389/fimmu.2021.729233
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author Guéry, Jean-Charles
author_facet Guéry, Jean-Charles
author_sort Guéry, Jean-Charles
collection PubMed
description Plasmacytoid dendritic cells (pDCs) produce type I interferon (IFN-I) during HIV-1 infection in response to TLR7 stimulation. However, IFN-I-signaling has been shown to play opposite effects in HIV-1 and SIV infection. TLR7-driven type I interferon production in pDCs is higher in women than in men due to the cell-intrinsic actions of estrogen and X-chromosome complement. Indeed, TLR7 is encoded on the X-chromosome, and the TLR7 gene escapes the X-chromosome inactivation in immune cells of women which express significantly higher levels of TLR7 protein than male cells. Following HIV infection, women have a lower viremia during acute infection and exhibit stronger antiviral responses than men, which has been attributed to the increased capacity of female pDCs to produce IFN-α upon TLR7-stimulation. However, a deleterious functional impact of an excessive TLR7 response on acute viremia in women has been recently revealed by the analysis of the frequent rs179008 c.32A>T SNP of TLR7. This SNP was identified as a sex-specific protein abundance quantitative trait locus (pQTL) causing a difference in the TLR7 protein dosage and effector function in females only. T allele expression was associated with a lower TLR7 protein synthesis, blunted production of IFN-α by pDCs upon TLR7 stimulation, and an unexpectedly lower viral load during primary HIV-1 infection in women. In the present review, the author will revisit the role of TLR7-driven pDC innate function in the context of HIV-1 infection to discuss at what stage of primary HIV-1 infection the TLR7 rs179008 T allele is likely to be protective in women.
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spelling pubmed-84329342021-09-11 Sex Differences in Primary HIV Infection: Revisiting the Role of TLR7-Driven Type 1 IFN Production by Plasmacytoid Dendritic Cells in Women Guéry, Jean-Charles Front Immunol Immunology Plasmacytoid dendritic cells (pDCs) produce type I interferon (IFN-I) during HIV-1 infection in response to TLR7 stimulation. However, IFN-I-signaling has been shown to play opposite effects in HIV-1 and SIV infection. TLR7-driven type I interferon production in pDCs is higher in women than in men due to the cell-intrinsic actions of estrogen and X-chromosome complement. Indeed, TLR7 is encoded on the X-chromosome, and the TLR7 gene escapes the X-chromosome inactivation in immune cells of women which express significantly higher levels of TLR7 protein than male cells. Following HIV infection, women have a lower viremia during acute infection and exhibit stronger antiviral responses than men, which has been attributed to the increased capacity of female pDCs to produce IFN-α upon TLR7-stimulation. However, a deleterious functional impact of an excessive TLR7 response on acute viremia in women has been recently revealed by the analysis of the frequent rs179008 c.32A>T SNP of TLR7. This SNP was identified as a sex-specific protein abundance quantitative trait locus (pQTL) causing a difference in the TLR7 protein dosage and effector function in females only. T allele expression was associated with a lower TLR7 protein synthesis, blunted production of IFN-α by pDCs upon TLR7 stimulation, and an unexpectedly lower viral load during primary HIV-1 infection in women. In the present review, the author will revisit the role of TLR7-driven pDC innate function in the context of HIV-1 infection to discuss at what stage of primary HIV-1 infection the TLR7 rs179008 T allele is likely to be protective in women. Frontiers Media S.A. 2021-08-27 /pmc/articles/PMC8432934/ /pubmed/34512664 http://dx.doi.org/10.3389/fimmu.2021.729233 Text en Copyright © 2021 Guéry https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Guéry, Jean-Charles
Sex Differences in Primary HIV Infection: Revisiting the Role of TLR7-Driven Type 1 IFN Production by Plasmacytoid Dendritic Cells in Women
title Sex Differences in Primary HIV Infection: Revisiting the Role of TLR7-Driven Type 1 IFN Production by Plasmacytoid Dendritic Cells in Women
title_full Sex Differences in Primary HIV Infection: Revisiting the Role of TLR7-Driven Type 1 IFN Production by Plasmacytoid Dendritic Cells in Women
title_fullStr Sex Differences in Primary HIV Infection: Revisiting the Role of TLR7-Driven Type 1 IFN Production by Plasmacytoid Dendritic Cells in Women
title_full_unstemmed Sex Differences in Primary HIV Infection: Revisiting the Role of TLR7-Driven Type 1 IFN Production by Plasmacytoid Dendritic Cells in Women
title_short Sex Differences in Primary HIV Infection: Revisiting the Role of TLR7-Driven Type 1 IFN Production by Plasmacytoid Dendritic Cells in Women
title_sort sex differences in primary hiv infection: revisiting the role of tlr7-driven type 1 ifn production by plasmacytoid dendritic cells in women
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432934/
https://www.ncbi.nlm.nih.gov/pubmed/34512664
http://dx.doi.org/10.3389/fimmu.2021.729233
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