Mass Cytometry Analysis Reveals Complex Cell-State Modifications of Blood Myeloid Cells During HIV Infection

Dendritic cells (DC), which are involved in orchestrating early immune responses against pathogens, are dysregulated in their function by HIV infection. This dysregulation likely contributes to tip the balance toward viral persistence. Different DC subpopulations, including classical (cDCs) and plasmacytoid (pDCs) dendritic cells, are subjected to concomitant inflammatory and immunoregulatory events during HIV infection, which hampers the precise characterization of their regulation through classical approaches. Here, we carried out mass cytometry analysis of blood samples from early HIV-infected patients that were longitudinally collected before and after 1 year of effective combination antiretroviral therapy (cART). Blood samples from HIV controller patients who naturally control the infection were also included. Our data revealed that plasma HIV RNA level was positively associated with a loss of cDC and pDC subpopulations that display high expression of LILR immunomodulatory receptors. Conversely, specific monocyte populations co-expressing high levels of HLA-I, 3 immunomodulatory receptors, CD64, LILRA2, and LILRB4, and the restriction factor CD317 (also known as BST2/Tetherin), were more abundant in early HIV-infection. Finally, our analysis revealed that the blood of HIV controller patients contained in a higher abundance a particular subtype of CD1c⁺ cDCs, characterized by elevated co-expression of CD32b inhibitory receptor and HLA-DR antigen-presentation molecules. Overall, this study unravels the modifications induced in DC and monocyte subpopulations in different HIV⁺ conditions, and provides a better comprehension of the immune regulation/dysregulation mechanisms induced during this viral infection.