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

doi:10.1016/j.isci.2023.107628

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

iScience. 2023 Aug 12;26(9):107628. doi: 10.1016/j.isci.2023.107628. eCollection 2023 Sep 15.

Authors

Lamin B Cham^{1

2}, Jesper D Gunst^{1

2}, Mariane H Schleimann^{1

2}, Giacomo S Frattari^{1

2}, Miriam Rosas-Umbert^{1

2}, Line K Vibholm¹, Renée M van der Sluis³, Martin R Jakobsen³, Rikke Olesen^{1

2}, Lin Lin³, Martin Tolstrup^{1

2}, Ole S Søgaard^{1

2}

Affiliations

¹ Department of Infectious Diseases, Aarhus University Hospital, 8200 Aarhus, Denmark.
² Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark.
³ Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark.

Abstract

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.

Keywords: Cell biology; Components of the immune system; Immunology; Transcriptomics.