Intestinal macrophages arising from CCR2(+) monocytes control pathogen infection by activating innate lymphoid cells.
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.
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, 1500 E Medical Center Dr Ann Arbor, Michigan 48109, USA.
Sang-Uk
SU
Seo
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, 1150 W Medical Center Dr, Ann Arbor, Michigan 48109, USA.
Peter
P
Kuffa
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, 1150 W Medical Center Dr, Ann Arbor, Michigan 48109, USA.
Sho
S
Kitamoto
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, 1150 W Medical Center Dr, Ann Arbor, Michigan 48109, USA.
Hiroko
H
Nagao-Kitamoto
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, 1150 W Medical Center Dr, Ann Arbor, Michigan 48109, USA.
Jenna
J
Rousseau
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, 1500 E Medical Center Dr Ann Arbor, Michigan 48109, USA.
Yun-Gi
YG
Kim
Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, 1500 E Medical Center Dr Ann Arbor, Michigan 48109, USA.
Gabriel
G
Núñez
Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, 1150 W Medical Center Dr, Ann Arbor, Michigan 48109, USA.
Nobuhiko
N
Kamada
D000818:Animals; D044082:Citrobacter rodentium / Q000502:physiology*; D004756:Enterobacteriaceae Infections / Q000276:immunology / Q000382:microbiology*; D007111:Immunity, Cellular; D007113:Immunity, Innate; D008214:Lymphocytes / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000145:classification* / Q000378:metabolism; D054390:Receptors, CCR2
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2