TY - JOUR
T1 - Immune activation of vaginal human Langerhans cells increases susceptibility to HIV-1 infection
AU - van Teijlingen, Nienke H.
AU - Eder, Julia
AU - Sarrami-Forooshani, Ramin
AU - Zijlstra-Willems, Esther M.
AU - Roovers, Jan-Paul W. R.
AU - van Leeuwen, Elisabeth
AU - Ribeiro, Carla M. S.
AU - Geijtenbeek, Teunis B. H.
N1 - Funding Information: This work was supported by the AMC PhD Scholarship, Dutch Research Council (NWO, http://www.nwo.nl/ ) VENI grant 863.13.025, NWO VICI grant 918.10.619, and the European Research Council ( https://erc.europa.eu/ ) Advanced Grant 670424. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2023, The Author(s).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Vaginal inflammation increases the risk for sexual HIV-1 transmission but underlying mechanisms remain unclear. In this study we assessed the impact of immune activation on HIV-1 susceptibility of primary human vaginal Langerhans cells (LCs). Vaginal LCs isolated from human vaginal tissue expressed a broad range of TLRs and became activated after exposure to both viral and bacterial TLR ligands. HIV-1 replication was restricted in immature vaginal LCs as only low levels of infection could be detected. Notably, activation of immature vaginal LCs by bacterial TLR ligands increased HIV-1 infection, whereas viral TLR ligands were unable to induce HIV-1 replication in vaginal LCs. Furthermore, mature vaginal LCs transmitted HIV-1 to CD4 T cells. This study emphasizes the role for vaginal LCs in protection against mucosal HIV-1 infection, which is abrogated upon activation. Moreover, our data suggest that bacterial STIs can increase the risk of HIV-1 acquisition in women.
AB - Vaginal inflammation increases the risk for sexual HIV-1 transmission but underlying mechanisms remain unclear. In this study we assessed the impact of immune activation on HIV-1 susceptibility of primary human vaginal Langerhans cells (LCs). Vaginal LCs isolated from human vaginal tissue expressed a broad range of TLRs and became activated after exposure to both viral and bacterial TLR ligands. HIV-1 replication was restricted in immature vaginal LCs as only low levels of infection could be detected. Notably, activation of immature vaginal LCs by bacterial TLR ligands increased HIV-1 infection, whereas viral TLR ligands were unable to induce HIV-1 replication in vaginal LCs. Furthermore, mature vaginal LCs transmitted HIV-1 to CD4 T cells. This study emphasizes the role for vaginal LCs in protection against mucosal HIV-1 infection, which is abrogated upon activation. Moreover, our data suggest that bacterial STIs can increase the risk of HIV-1 acquisition in women.
UR - http://www.scopus.com/inward/record.url?scp=85149037316&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41598-023-30097-x
DO - https://doi.org/10.1038/s41598-023-30097-x
M3 - Article
C2 - 36841916
SN - 2045-2322
VL - 13
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 3283
ER -