Single cell analysis reveals a subset of cytotoxic-like plasmacytoid dendritic cells in people with HIV-1
Lamin B. Cham,
Jesper D. Gunst,
Mariane H. Schleimann,
Giacomo S. Frattari,
Miriam Rosas-Umbert,
Line K. Vibholm,
Renée M. van der Sluis,
Martin R. Jakobsen,
Rikke Olesen,
Lin Lin,
Martin Tolstrup,
Ole S. Søgaard
Affiliations
Lamin B. Cham
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark
Jesper D. Gunst
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark
Mariane H. Schleimann
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark
Giacomo S. Frattari
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark
Miriam Rosas-Umbert
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark
Line K. Vibholm
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark
Renée M. van der Sluis
Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark
Martin R. Jakobsen
Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark
Rikke Olesen
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark
Lin Lin
Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark
Martin Tolstrup
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark
Ole S. Søgaard
Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark; Corresponding author
Summary: 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.
