Vaginal bacterium Prevotella timonensis turns protective Langerhans cells into HIV-1 reservoirs for virus dissemination.

Autor: van Teijlingen NH; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam institute for Infection and Immunity, Amsterdam, The Netherlands., Helgers LC; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam institute for Infection and Immunity, Amsterdam, The Netherlands., Sarrami-Forooshani R; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; ATMP Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran., Zijlstra-Willems EM; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam institute for Infection and Immunity, Amsterdam, The Netherlands., van Hamme JL; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam institute for Infection and Immunity, Amsterdam, The Netherlands., Segui-Perez C; Division Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands., van Smoorenburg MY; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam institute for Infection and Immunity, Amsterdam, The Netherlands., Borgdorff H; Amsterdam Institute for Global Health and Development (AIGHD), Amsterdam, The Netherlands., van de Wijgert JH; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., van Leeuwen E; Department of Obstetrics and Gynecology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., van der Post JA; Department of Obstetrics and Gynecology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands., Strijbis K; Division Infectious Diseases and Immunology, Department of Biomolecular Health Sciences, Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands., Ribeiro CM; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam institute for Infection and Immunity, Amsterdam, The Netherlands., Geijtenbeek TB; Department of Experimental Immunology, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.; Amsterdam institute for Infection and Immunity, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2022 Oct 04; Vol. 41 (19), pp. e110629. Date of Electronic Publication: 2022 Aug 15.
DOI: 10.15252/embj.2022110629
Abstrakt: Dysbiosis of vaginal microbiota is associated with increased HIV-1 acquisition, but the underlying cellular mechanisms remain unclear. Vaginal Langerhans cells (LCs) protect against mucosal HIV-1 infection via autophagy-mediated degradation of HIV-1. As LCs are in continuous contact with bacterial members of the vaginal microbiome, we investigated the impact of commensal and dysbiosis-associated vaginal (an)aerobic bacterial species on the antiviral function of LCs. Most of the tested bacteria did not affect the HIV-1 restrictive function of LCs. However, Prevotella timonensis induced a vast uptake of HIV-1 by vaginal LCs. Internalized virus remained infectious for days and uptake was unaffected by antiretroviral drugs. P. timonensis-exposed LCs efficiently transmitted HIV-1 to target cells both in vitro and ex vivo. Additionally, P. timonensis exposure enhanced uptake and transmission of the HIV-1 variants that establish infection after sexual transmission, the so-called Transmitted Founder variants. Our findings, therefore, suggest that P. timonensis might set the stage for enhanced HIV-1 susceptibility during vaginal dysbiosis and advocate targeted treatment of P. timonensis during bacterial vaginosis to limit HIV-1 infection.
(© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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