Intestinal macrophages arising from CCR2+ monocytes control pathogen infection by activating innate lymphoid cells

Sang Uk Seo, Peter Kuffa, Sho Kitamoto, Hiroko Nagao-Kitamoto, Jenna Rousseau, Yungi Kim, Gabriel Núñez, Nobuhiko Kamada

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Monocytes play a crucial role in antimicrobial host defence, but the mechanisms by which they protect the host during intestinal infection remains poorly understood. Here we show that depletion of CCR2+ monocytes results in impaired clearance of the intestinal pathogen Citrobacter rodentium. After infection, the de novo recruited CCR2+ monocytes give rise to CD11c+ CD11b+ F4/80+ CD103- intestinal macrophages (MPs) within the lamina propria. Unlike resident intestinal MPs, de novo differentiated MPs are phenotypically pro-inflammatory and produce robust amounts of IL-1β (interleukin-1β) through the non-canonical caspase-11 inflammasome. Intestinal MPs from infected mice elicit the activation of RORγt+ group 3 innate lymphoid cells (ILC3) in an IL-1β-dependent manner. Deletion of IL-1β in blood monocytes blunts the production of IL-22 by ILC3 and increases the susceptibility to infection. Collectively, these studies highlight a critical role of de novo differentiated monocyte-derived intestinal MPs in ILC3-mediated host defence against intestinal infection.

Original languageEnglish
Article number8010
JournalNature Communications
Volume6
DOIs
Publication statusPublished - 2015 Aug 13
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

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    Seo, S. U., Kuffa, P., Kitamoto, S., Nagao-Kitamoto, H., Rousseau, J., Kim, Y., Núñez, G., & Kamada, N. (2015). Intestinal macrophages arising from CCR2+ monocytes control pathogen infection by activating innate lymphoid cells. Nature Communications, 6, [8010]. https://doi.org/10.1038/ncomms9010