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, Yun Gi Kim, Gabriel Núñez, Nobuhiko Kamada

Research output: Contribution to journalArticleResearchpeer-review

28 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
StatePublished - 13 Aug 2015

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monocytes
macrophages
pathogens
Macrophages
Pathogens
infectious diseases
Infection Control
Monocytes
interleukins
Lymphocytes
Interleukin-1
cells
Infection
Citrobacter rodentium
Inflammasomes
deletion
clearances
Caspases
blood
mice

Cite this

Seo, S-U., Kuffa, P., Kitamoto, S., Nagao-Kitamoto, H., Rousseau, J., Kim, Y. 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
Seo, Sang-Uk ; Kuffa, Peter ; Kitamoto, Sho ; Nagao-Kitamoto, Hiroko ; Rousseau, Jenna ; Kim, Yun Gi ; Núñez, Gabriel ; Kamada, Nobuhiko. / Intestinal macrophages arising from CCR2+ monocytes control pathogen infection by activating innate lymphoid cells. In: Nature Communications. 2015 ; Vol. 6.
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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.",
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Seo, S-U, Kuffa, P, Kitamoto, S, Nagao-Kitamoto, H, Rousseau, J, Kim, YG, Núñez, G & Kamada, N 2015, 'Intestinal macrophages arising from CCR2+ monocytes control pathogen infection by activating innate lymphoid cells', Nature Communications, vol. 6, 8010. https://doi.org/10.1038/ncomms9010

Intestinal macrophages arising from CCR2+ monocytes control pathogen infection by activating innate lymphoid cells. / Seo, Sang-Uk; Kuffa, Peter; Kitamoto, Sho; Nagao-Kitamoto, Hiroko; Rousseau, Jenna; Kim, Yun Gi; Núñez, Gabriel; Kamada, Nobuhiko.

In: Nature Communications, Vol. 6, 8010, 13.08.2015.

Research output: Contribution to journalArticleResearchpeer-review

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