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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Mucosal Immunity
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1472656

Human genital dendritic cell heterogeneity confers differential rapid response to HIV-1 exposure

Provisionally accepted
Siddharth Parthasarathy Siddharth Parthasarathy 1Laura Moreno De Lara Laura Moreno De Lara 1Francisco Carrillo-Salinas Francisco Carrillo-Salinas 1Alexandra Werner Alexandra Werner 1Anna Borchers Anna Borchers 1Vidya Iyer Vidya Iyer 2Alison Vogell Alison Vogell 2Jared M. Fortier Jared M. Fortier 3Charles Wira Charles Wira 4Marta Rodriguez-Garcia Marta Rodriguez-Garcia 3*
  • 1 School of Medicine, Tufts University, Boston, Massachusetts, United States
  • 2 Tufts Medical Center, Boston, Massachusetts, United States
  • 3 Wayne State University, Detroit, Michigan, United States
  • 4 Geisel School of Medicine, Dartmouth College, Hanover, New Hampshire, United States

The final, formatted version of the article will be published soon.

    Dendritic cells (DCs) play critical roles in HIV pathogenesis and require further investigation in the female genital tract, a main portal of entry for HIV infection. Here we characterized genital DC populations at the single cell level and how DC subsets respond to HIV immediately following exposure. We found that the genital CD11c + HLA-DR + myeloid population contains three DC subsets (CD1c+ DC2s, CD14+ monocyte-derived DCs and CD14 + CD1c + DC3s) and two monocyte/macrophage populations with distinct functional and phenotypic properties during homeostasis. Following HIV exposure, the antiviral response was dominated by DCs' rapid secretory response, activation of non-classical inflammatory pathways and host restriction factors.Further, we uncovered subset-specific differences in anti-HIV responses. CD14+ DCs were the main population activated by HIV and mediated the secretory antimicrobial response, while CD1c+ DC2s activated inflammasome pathways and IFN responses. Identification of subsetspecific responses to HIV immediately after exposure could aid targeted strategies to prevent HIV infection.

    Keywords: dendritic cell, HIV, female genital tract, single-cell RNA sequencing, mucosal immunity, antiviral response

    Received: 29 Jul 2024; Accepted: 03 Oct 2024.

    Copyright: © 2024 Parthasarathy, Moreno De Lara, Carrillo-Salinas, Werner, Borchers, Iyer, Vogell, Fortier, Wira and Rodriguez-Garcia. 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) or licensor 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.

    * Correspondence: Marta Rodriguez-Garcia, Wayne State University, Detroit, 48202, Michigan, United States

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