Abstract
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.
Highlights
HIV infection is characterized by the dysregulation of immune responses leading to viral persistence and disease progression [1,2,3]
The production of soluble CD14 and CD163, which reflects monocyte/macrophage activation, has been associated with HIV mortality in primary and chronic infection [3, 15,16,17]. Even though these studies indicate that Dendritic cells (DC) and monocyte subpopulations are dysregulated in HIV infection, a precise view of their dysregulation mechanisms at the molecular level is difficult to decipher through classical approaches
To characterize the phenotypic diversity of DC and monocyte subsets in HIV primary and controlled infections, we developed a mass-cytometry panel of 29 markers mainly dedicated to myeloid cells (Table S1)
Summary
HIV infection is characterized by the dysregulation of immune responses leading to viral persistence and disease progression [1,2,3]. Several studies indicate that in HIV or SIV infections, cDCs are prone to apoptosis and demonstrate attenuated capacities of antigen presentation and cytokine production leading to inefficient T-cell proliferation [1, 6,7,8]. Further studies in rhesus macaques identify dysregulation of cDCs induced in early SIV infection as a predictive marker of disease progression [11]. These studies suggest a critical role for cDCs in the regulation of early immune responses, where deficiencies in functions tip the balance of disease outcomes toward viral persistence
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