PMID- 36949942 OWN - NLM STAT- MEDLINE DCOM- 20230324 LR - 20230328 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 14 DP - 2023 TI - Transmission of Zika virus by dendritic cell subsets in skin and vaginal mucosa. PG - 1125565 LID - 10.3389/fimmu.2023.1125565 [doi] LID - 1125565 AB - Zika virus is a member of the Flaviviridae family that has caused recent outbreaks associated with neurological malformations. Transmission of Zika virus occurs primarily via mosquito bite but also via sexual contact. Dendritic cells (DCs) and Langerhans cells (LCs) are important antigen presenting cells in skin and vaginal mucosa and paramount to induce antiviral immunity. To date, little is known about the first cells targeted by Zika virus in these tissues as well as subsequent dissemination of the virus to other target cells. We therefore investigated the role of DCs and LCs in Zika virus infection. Human monocyte derived DCs (moDCs) were isolated from blood and primary immature LCs were obtained from human skin and vaginal explants. Zika virus exposure to moDCs but not skin and vaginal LCs induced Type I Interferon responses. Zika virus efficiently infected moDCs but neither epidermal nor vaginal LCs became infected. Infection of a human full skin model showed that DC-SIGN expressing dermal DCs are preferentially infected over langerin+ LCs. Notably, not only moDCs but also skin and vaginal LCs efficiently transmitted Zika virus to target cells. Transmission by LCs was independent of direct infection of LCs. These data suggest that DCs and LCs are among the first target cells for Zika virus not only in the skin but also the genital tract. The role of vaginal LCs in dissemination of Zika virus from the vaginal mucosa further emphasizes the threat of sexual transmission and supports the investigation of prophylaxes that go beyond mosquito control. CI - Copyright (c) 2023 Eder, Zijlstra-Willems, Koen, Kootstra, Wolthers and Geijtenbeek. FAU - Eder, Julia AU - Eder J AD - Department of Experimental Immunology, Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands. AD - Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands. FAU - Zijlstra-Willems, Esther AU - Zijlstra-Willems E AD - Department of Experimental Immunology, Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands. FAU - Koen, Gerrit AU - Koen G AD - Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands. FAU - Kootstra, Neeltje A AU - Kootstra NA AD - Department of Experimental Immunology, Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands. AD - Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands. FAU - Wolthers, Katja C AU - Wolthers KC AD - Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands. FAU - Geijtenbeek, Teunis B AU - Geijtenbeek TB AD - Department of Experimental Immunology, Amsterdam UMC location University of Amsterdam, Amsterdam, Netherlands. AD - Amsterdam Institute for Infection and Immunity, Amsterdam, Netherlands. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230306 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 SB - IM MH - Female MH - Humans MH - Dendritic Cells MH - *Zika Virus MH - Langerhans Cells MH - Epidermis/metabolism MH - Mucous Membrane MH - *Zika Virus Infection/metabolism PMC - PMC10025456 OTO - NOTNLM OT - Langerhans cells OT - Zika virus OT - vaginal mucosa OT - viral dissemination OT - virus transmission COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/03/24 06:00 MHDA- 2023/03/25 06:00 PMCR- 2023/01/01 CRDT- 2023/03/23 02:18 PHST- 2022/12/16 00:00 [received] PHST- 2023/02/23 00:00 [accepted] PHST- 2023/03/23 02:18 [entrez] PHST- 2023/03/24 06:00 [pubmed] PHST- 2023/03/25 06:00 [medline] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2023.1125565 [doi] PST - epublish SO - Front Immunol. 2023 Mar 6;14:1125565. doi: 10.3389/fimmu.2023.1125565. eCollection 2023.