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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Acne Vulgaris / immunology*
  • Acne Vulgaris / microbiology
  • Animals
  • Antigen Presentation
  • Chemotaxis, Leukocyte / immunology
  • Dendritic Cells / classification*
  • Dendritic Cells / immunology
  • Ear, External
  • Gene Expression Regulation
  • Gene Ontology
  • Gram-Positive Bacterial Infections / immunology*
  • Gram-Positive Bacterial Infections / microbiology
  • Humans
  • Injections, Intradermal
  • Mice
  • Mice, Inbred C57BL
  • Neutrophil Infiltration / immunology*
  • Neutrophils / metabolism
  • Propionibacterium acnes
  • RNA, Messenger / biosynthesis
  • Single-Cell Analysis
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / immunology*

Substances

  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse