Single cell transcriptomic atlas of human plasmacytoid dendritic cells reveals a distinct cytotoxic-like subset in HIV-1 infected individuals.
To understand how the transcriptome of pDCs is impacted by HIV-1 infection and exogenous stimulation, we sorted pDCs from people with HIV-1 (PWH) on antiretroviral treatment before and after toll-like receptor 9 (TLR9) agonist treatment, as well as from healthy controls, and performed single-cell (sc)-RNA sequencing. We generated a transcriptomic atlas of over 112,000 pDCs. Our cluster analysis revealed an inducible cytotoxic-like pDC cluster characterized by high expression of both antiviral and cytotoxic genes. We further reported that this cytotoxic-like pDC cluster is distinct from NK and T cells. This observation was further supported by our cell-cell communication analysis revealing that cytotoxic-like pDCs exhibit similar incoming and outgoing cellular communicating signals as other pDCs. In addition to the cytotoxic-like pDC cluster, we also characterized two homogenous pDC clusters (pDC1 and pDC2) and an exhausted pDC cluster. In conclusion, our findings provide a comprehensive pDC transcriptomic atlas and open a new scope on the mechanisms of regulation and function of cytotoxic-like pDCs in HIV and other infections. Overall design: we sorted pDCs from people with HIV-1 (PWH) on antiretroviral treatment before and after toll-like receptor 9 (TLR9) agonist treatment, as well as from healthy controls, and performed single-cell (sc)-RNA sequencing