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Immunity. 2019 Apr 16;50(4):1069-1083.e8. doi: 10.1016/j.immuni.2019.03.001. Epub 2019 Mar 27.

A Subset of Type I Conventional Dendritic Cells Controls Cutaneous Bacterial Infections through VEGFα-Mediated Recruitment of Neutrophils.

Author information

1
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, Biopolis, Singapore 138648, Singapore; Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A(∗)STAR), 11 Mandalay Rd., Singapore 308232, Singapore.
2
Division of Medicine, University College London, University of London, London WC1E 6BT, England, UK.
3
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, Biopolis, Singapore 138648, Singapore.
4
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, Biopolis, Singapore 138648, Singapore; Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore.
5
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, Biopolis, Singapore 138648, Singapore; Nestlé Skin Health R&D/GALDERMA, La Tour-de-Peilz 1814, Switzerland.
6
Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110, USA.
7
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS UMR, Marseille 13288, France.
8
Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, INSERM, CNRS UMR, Marseille 13288, France; Centre d'Immunophénomique, Aix Marseille Université, INSERM, CNRS, Marseille 13288, France.
9
Transgenic Mouse Core Facility, VIB-UGnet Center for Inflammation Research, Technologiepark 71, Ghent 9052, Belgium; Department of Biomedical Molecular Biology, Ghent University, Technologiepark 71, Ghent 9052, Belgium.
10
Department of Biomedical Molecular Biology, Ghent University, Technologiepark 71, Ghent 9052, Belgium; Laboratory of Myeloid Cell Ontogeny and Functional Specialization, VIB-UGnet Center for Inflammation Research, Technologiepark 71, Ghent 9052, Belgium.
11
Nestlé Skin Health R&D/GALDERMA, La Tour-de-Peilz 1814, Switzerland.
12
Department of Dermatology, Avicenne Hospital and INSERM U1125, Bobigny 93000, France.
13
Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, Biopolis, Singapore 138648, Singapore; Skin Research Institute of Singapore (SRIS), Agency for Science, Technology and Research (A(∗)STAR), 11 Mandalay Rd., Singapore 308232, Singapore. Electronic address: florent_ginhoux@immunol.a-star.edu.sg.

Abstract

Skin conventional dendritic cells (cDCs) exist as two distinct subsets, cDC1s and cDC2s, which maintain the balance of immunity to pathogens and tolerance to self and microbiota. Here, we examined the roles of dermal cDC1s and cDC2s during bacterial infection, notably Propionibacterium acnes (P. acnes). cDC1s, but not cDC2s, regulated the magnitude of the immune response to P. acnes in the murine dermis by controlling neutrophil recruitment to the inflamed site and survival and function therein. Single-cell mRNA sequencing revealed that this regulation relied on secretion of the cytokine vascular endothelial growth factor α (VEGF-α) by a minor subset of activated EpCAM+CD59+Ly-6D+ cDC1s. Neutrophil recruitment by dermal cDC1s was also observed during S. aureus, bacillus Calmette-Guérin (BCG), or E. coli infection, as well as in a model of bacterial insult in human skin. Thus, skin cDC1s are essential regulators of the innate response in cutaneous immunity and have roles beyond classical antigen presentation.

KEYWORDS:

VEGF; VEGFR; XCR1; activation; cDC1; dendritic cell; langerin; monocyte; neutrophil; recruitment

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