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 | |
| Publication status | Published - 2015 Aug 13 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Chemistry(all)
- Physics and Astronomy(all)
Cite this
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, Yungi; Núñez, Gabriel; Kamada, Nobuhiko.
In: Nature Communications, Vol. 6, 8010, 13.08.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Intestinal macrophages arising from CCR2+ monocytes control pathogen infection by activating innate lymphoid cells
AU - Seo, Sang Uk
AU - Kuffa, Peter
AU - Kitamoto, Sho
AU - Nagao-Kitamoto, Hiroko
AU - Rousseau, Jenna
AU - Kim, Yungi
AU - Núñez, Gabriel
AU - Kamada, Nobuhiko
PY - 2015/8/13
Y1 - 2015/8/13
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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U2 - 10.1038/ncomms9010
DO - 10.1038/ncomms9010
M3 - Article
C2 - 26269452
AN - SCOPUS:84939166338
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 8010
ER -