Complement C5a promotes antigen cross-presentation by Peyer's patch monocyte-derived dendritic cells and drives a protective CD8+ T cell response

Cell Rep. 2021 Apr 13;35(2):108995. doi: 10.1016/j.celrep.2021.108995.

Abstract

The complement fragment C5a is closely associated with adaptive immune induction in the mucosa. However, the mechanisms that control CD8+ T cell responses by C5a have not been extensively explored. This study reveals that C5/C5a in the Peyer's patch (PP) subepithelial dome increases upon oral Listeria infection. We hypothesize that C5aR+ PP cells play an important role in the induction of antigen-specific T cell immunity. Using single-cell RNA sequencing, we identify C5aR- and lysozyme-expressing dendritic cells (C5aR+ LysoDCs) in PP and examine their role in CD8+ T cell immune induction. Stimulation of C5aR+ LysoDCs by C5a increases reactive oxygen species levels, leading to efficient antigen cross-presentation, which elicits an antigen-specific CD8+ T cell response. In C5-deficient mice, oral co-administration of C5a and Listeria enhances Listeria-specific cytotoxic T cell levels. Collectively, these findings suggest a role of the complement system in intestinal T cell immunity.

Keywords: C5a receptor; CD8(+) T cell; Peyer’s patch; complement C5a; cross-presentation; dendritic cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antigen Presentation
  • Complement C5a / genetics
  • Complement C5a / immunology*
  • Complement C5a / pharmacology
  • Cross-Priming*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / microbiology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Immunity, Mucosal
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / microbiology
  • Listeria monocytogenes / immunology*
  • Listeria monocytogenes / pathogenicity
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / microbiology
  • Muramidase / genetics
  • Muramidase / immunology
  • Peyer's Patches / drug effects
  • Peyer's Patches / immunology*
  • Peyer's Patches / microbiology
  • Reactive Oxygen Species / immunology
  • Reactive Oxygen Species / metabolism
  • Receptor, Anaphylatoxin C5a / genetics*
  • Receptor, Anaphylatoxin C5a / immunology
  • Single-Cell Analysis
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / microbiology

Substances

  • Reactive Oxygen Species
  • Receptor, Anaphylatoxin C5a
  • Complement C5a
  • Muramidase