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

Nienke H. van Teijlingen, Leanne C. Helgers, Ramin Sarrami-Forooshani, Esther M. Zijlstra-Willems, John L. van Hamme, Celia Segui-Perez, Marleen Y. van Smoorenburg, Hanneke Borgdorff, Janneke H. HM van de Wijgert, Elisabeth van Leeuwen, Joris A. M. van der Post, Karin Strijbis, Carla M. S. Ribeiro, Teunis B. H. Geijtenbeek

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5 Citations (Scopus)

Abstract

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.
Original languageEnglish
Article numbere110629
JournalEMBO Journal
Volume41
Issue number19
Early online date2022
DOIs
Publication statusPublished - 4 Oct 2022

Keywords

  • HIV-1
  • Langerhans cells (LCs)
  • Prevotella timonensis
  • transmission
  • vaginal microbiome

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