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

TY - JOUR

T1 - Single cell analysis reveals a subset of cytotoxic-like plasmacytoid dendritic cells in people with HIV-1

AU - Cham, Lamin B.

AU - Gunst, Jesper D.

AU - Schleimann, Mariane H.

AU - Frattari, Giacomo S.

AU - Rosas-Umbert, Miriam

AU - Vibholm, Line K.

AU - van der Sluis, Renée M.

AU - Jakobsen, Martin R.

AU - Olesen, Rikke

AU - Lin, Lin

AU - Tolstrup, Martin

AU - Søgaard, Ole S.

PY - 2023/9

Y1 - 2023/9

N2 - 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.

AB - 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.

KW - Cell biology

KW - Components of the immune system

KW - Immunology

KW - Transcriptomics

UR - http://www.scopus.com/inward/record.url?scp=85170273733&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2023.107628

DO - 10.1016/j.isci.2023.107628

M3 - Journal article

C2 - 37664600

AN - SCOPUS:85170273733

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 9

M1 - 107628

ER -