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

doi:10.1038/ncomms9010

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 journal › Article › peer-review

47 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 language	English
Article number	8010
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9010
Publication status	Published - 2015 Aug 13
Externally published	Yes

ASJC Scopus subject areas

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

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10.1038/ncomms9010

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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 journal › Article › peer-review

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title = "Intestinal macrophages arising from CCR2+ monocytes control pathogen infection by activating innate lymphoid cells",

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.",

author = "Seo, {Sang Uk} and Peter Kuffa and Sho Kitamoto and Hiroko Nagao-Kitamoto and Jenna Rousseau and Kim, {Yun Gi} and Gabriel N{\'u}{\~n}ez and Nobuhiko Kamada",

note = "Funding Information: The authors thank Drs Mo El-Zaatari, Helmut Grasberger, Andrew Shreiner and John Kao for helpful discussion, Joel Whitfield of the University of Michigan Immunology Core for performing ELISAs, Dahai Yang and Yuan He for caspase-11 immunoblotting, and Melody Zeng and Judith Connett for critical reading of the manuscript. This work was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology 2013R1A6A3A03024348 (S.-U. S), JSPS Postdoctoral Fellow for Research Abroad (S. K. and H. N.-K.), Career Development Awards from the Crohn{\textquoteright}s and Colitis Foundation of America (Y.-G. K and N. K.), Michigan Gastrointestinal Peptide Research Center NIDDK DK034933 (N. K.), NIH grants DK091191 and DK095782 (G. N.). Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",

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AU - Seo, Sang Uk

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AU - Rousseau, Jenna

AU - Kim, Yun Gi

AU - Núñez, Gabriel

AU - Kamada, Nobuhiko

N1 - Funding Information: The authors thank Drs Mo El-Zaatari, Helmut Grasberger, Andrew Shreiner and John Kao for helpful discussion, Joel Whitfield of the University of Michigan Immunology Core for performing ELISAs, Dahai Yang and Yuan He for caspase-11 immunoblotting, and Melody Zeng and Judith Connett for critical reading of the manuscript. This work was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology 2013R1A6A3A03024348 (S.-U. S), JSPS Postdoctoral Fellow for Research Abroad (S. K. and H. N.-K.), Career Development Awards from the Crohn’s and Colitis Foundation of America (Y.-G. K and N. K.), Michigan Gastrointestinal Peptide Research Center NIDDK DK034933 (N. K.), NIH grants DK091191 and DK095782 (G. N.). Publisher Copyright: © 2015 Macmillan Publishers Limited. All rights reserved.

PY - 2015/8/13

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N2 - 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.

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

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