RALDH Activity Induced by Bacterial/Fungal Pathogens in CD16+ Monocyte-Derived Dendritic Cells Boosts HIV Infection and Outgrowth in CD4+ T Cells

Abstract HIV reservoirs persist in gut-homing CD4+ T cells of people living with and receiving antiretroviral therapy, but the antigenic specificity such remains poorly documented. The imprinting for gut homing is mediated by retinoic acid (RA), a vitamin A–derived metabolite produced dendritic (DCs) exhibiting RA-synthesizing (RALDH) activity. RALDH activity DCs can be induced TLR2 ligands, as bacterial peptidoglycans fungal zymosan. Thus, we hypothesized that bacterial/fungal pathogens triggering fuel reservoir establishment/outgrowth pathogen-reactive cells. Our results demonstrate derived from intermediate/nonclassical CD16+ compared classical CD16− monocytes exhibited superior higher capacity to transmit infection autologous Staphylococcus aureus–reactive Exposure total monocyte-derived (MDDCs) S. aureus lysates well (zymosan heat-killed preparation Listeria monocytogenes) TLR4 (LPS) agonists not CMV resulted robust upregulation MDDCs loaded or zymosan proliferation CCR5+integrin β7+CCR6+ phenotype efficiently transmitted these via RALDH/RA–dependent mechanisms. Finally, aureus– zymosan-reactive therapy-treated carried replication-competent integrated HIV-DNA, demonstrated an MDDC-based viral outgrowth assay. Together, support model which promote MDDCs, especially subsequently imprint potential permissiveness. nonviral play key roles fueling mechanisms may therapeutically targeted.