Retinoic acid enhances HIV-1 reverse transcription and transcription in macrophages via mTOR-modulated mechanisms.

The intestinal environment facilitates HIV-1 infection via mechanisms involving the gut-homing vitamin A-derived retinoic acid (RA), which transcriptionally reprograms CD4 T cells for increased HIV-1 replication/outgrowth. Consistently, colon-infiltrating CD4 T cells carry replication-competent viral reservoirs in people with HIV-1 (PWH) receiving antiretroviral therapy (ART). Intriguingly, integrative infection in colon macrophages, a pool replenished by monocytes, represents a rare event in ART-treated PWH, thus questioning the effect of RA on macrophages.

Flow Cytometry Sorting of Memory CCR6CD4 T-Cells for HIV Reservoir Quantification.

Antiretroviral therapy (ART) has transformed the deadly human immunodeficiency virus type I (HIV-1) epidemic into a manageable chronic condition. Current ART is not curative and treatment interruption leads to viral rebound in people living with HIV-1 (PLWH). The main cause of viral rebound is the persistence of HIV reservoirs in long-lived memory CD4 T cells.

Antiretroviral Drug Transporters and Metabolic Enzymes in Circulating Monocytes and Monocyte-Derived Macrophages of ART-Treated People Living With HIV and HIV-Uninfected Individuals.

Membrane-associated drug transport proteins and drug metabolic enzymes could regulate intracellular antiretroviral (ARV) drug concentrations in HIV-1 target cells such as myeloid cells. We investigated the expression of these transporters and enzymes in monocyte subsets and monocyte-derived macrophages (MDMs) isolated from peripheral blood mononuclear cells (PBMCs) of HIV-uninfected individuals (HIV-negative) and people living with HIV receiving viral suppressive antiretroviral therapy (ART; HIV+ART) and examined plasma and intracellular ARV concentrations. Monocytes were isolated from PBMCs of 12 HIV-negative and 12 HIV+ART donors and differentiated into MDMs.

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

HIV reservoirs persist in gut-homing CD4 T cells of people living with HIV and receiving antiretroviral therapy, but the antigenic specificity of such reservoirs remains poorly documented. The imprinting for gut homing is mediated by retinoic acid (RA), a vitamin A-derived metabolite produced by dendritic cells (DCs) exhibiting RA-synthesizing (RALDH) activity. RALDH activity in DCs can be induced by TLR2 ligands, such as bacterial peptidoglycans and fungal zymosan.

Daily variations of gut microbial translocation markers in ART-treated HIV-infected people.

Background: Increased intestinal barrier permeability and subsequent gut microbial translocation are significant contributors to inflammatory non-AIDS comorbidities in people living with HIV (PLWH). Evidence in animal models have shown that markers of intestinal permeability and microbial translocation vary over the course of the day and are affected by food intake and circadian rhythms. However, daily variations of these markers are not characterized yet in PLWH.

HIV-1 is rarely detected in blood and colon myeloid cells during viral-suppressive antiretroviral therapy.

Objective: The aim of this study was to explore the contribution of blood and colon myeloid cells to HIV persistence during antiretroviral therapy (ART).

Design: Leukapheresis was collected from HIV-infected individuals with undetectable plasma viral load during ART (HIV + ART; n = 15) and viremics untreated (HIV+; n = 6). Rectal sigmoid biopsies were collected from n = 8 HIV+ART.

CD16 monocytes give rise to CD103RALDH2TCF4 dendritic cells with unique transcriptional and immunological features.

Classical CD16 vs intermediate/nonclassical CD16 monocytes differ in their homing potential and biological functions, but whether they differentiate into dendritic cells (DCs) with distinct contributions to immunity against bacterial/viral pathogens remains poorly investigated. Here, we employed a systems biology approach to identify clinically relevant differences between CD16 and CD16 monocyte-derived DCs (MDDCs). Although both CD16 and CD16 MDDCs acquire classical immature/mature DC markers in vitro, genome-wide transcriptional profiling revealed unique molecular signatures for CD16 MDDCs, including adhesion molecules (ITGAE/CD103), transcription factors (TCF7L2/TCF4), and enzymes (ALDH1A2/RALDH2), whereas CD16 MDDCs exhibit a CDH1/E-cadherin phenotype.