Single cell analysis reveals a subset of cytotoxic-like plasmacytoid dendritic cells in people with HIV-1

Human plasmacytoid dendritic cells (pDCs) play a central role in initiating and activating host immune responses during infection. To understand how the transcriptome of pDCs is impacted by HIV-1 infection and exogenous stimulation, we isolated pDCs from healthy controls, people with HIV-1 (PWH) before and during toll-like receptor 9 (TLR9) agonist treatment and performed single-cell (sc)-RNA sequencing. Our cluster analysis revealed four pDC clusters: pDC1, pDC2, cytotoxic-like pDC and an exhausted pDC cluster. The inducible cytotoxic-like pDC cluster is characterized by high expression of both antiviral and cytotoxic genes. Further analyses confirmed that cytotoxic-like pDCs are distinct from NK and T cells. Cell-cell communication analysis also demonstrated that cytotoxic-like pDCs exhibit similar incoming and outgoing cellular communicating signals as other pDCs. Thus, our study presents a detailed transcriptomic atlas of pDCs and provides new perspectives on the mechanisms of regulation and function of cytotoxic-like pDCs.