Dataset Information

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.

SUBMITTER: Seo SU

PROVIDER: S-EPMC4536571 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Insights into mechanisms governing resolution of inflammatory pain are of great importance for many chronic pain-associated diseases. Here we investigate the role of macrophages/monocytes and the anti-inflammatory cytokine interleukin-10 (IL-10) in the resolution of transient inflammatory pain. Depletion of mice from peripheral monocytes/macrophages delayed resolution of intraplantar IL-1?- and carrageenan-induced inflammatory hyperalgesia from 1 to 3 days to >1 week. Intrathecal administration of a neutralizing IL-10 antibody also markedly delayed resolution of IL-1?- and carrageenan-induced inflammatory hyperalgesia. Recently, we showed that IL-1?- and carrageenan-induced hyperalgesia is significantly prolonged in LysM-GRK2(+/-) mice, which have reduced levels of G-protein-coupled receptor kinase 2 (GRK2) in LysM(+) myeloid cells. Here we show that adoptive transfer of wild-type, but not of GRK2(+/-), bone marrow-derived monocytes normalizes the resolution of IL-1?-induced hyperalgesia in LysM-GRK2(+/-) mice. Adoptive transfer of IL-10(-/-) bone marrow-derived monocytes failed to normalize the duration of IL-1?-induced hyperalgesia in LysM-GRK2(+/-) mice. Mechanistically, we show that GRK2(+/-) macrophages produce less IL-10 in vitro. In addition, intrathecal IL-10 administration attenuated IL-1?-induced hyperalgesia in LysM-GRK2(+/-) mice, whereas it had no effect in wild-type mice. Our data uncover a key role for monocytes/macrophages in promoting resolution of inflammatory hyperalgesia via a mechanism dependent on IL-10 signaling in dorsal root ganglia.We show that IL-10-producing monocytes/macrophages promote resolution of transient inflammatory hyperalgesia. Additionally, we show that reduced monocyte/macrophage GRK2 impairs resolution of hyperalgesia and reduces IL-10 production. We propose that low GRK2 expression and/or impaired IL-10 production by monocytes/macrophages represent peripheral biomarkers for the risk of developing chronic pain after inflammation.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure