Commensal microbiota induce LPS hyporesponsiveness in colonic macrophages via the production of IL-10

Several subsets of innate immune cells, all with unique properties, reside within the intestinal lamina propria. However, compared with intestinal dendritic cells (DCs), intestinal macrophages are less well characterized. In this study, we examined the properties of macrophages in the colonic lamina propria (LM phi). Colonic DCs (LDC) showed LPS-induced production of IL-12p40. In contrast, LM phi showed constitutive IL-10 production and unresponsiveness to LPS in terms of inflammatory cytokine production. Comparison of the gene expression profiles between LM phi and LDC revealed that LM phi preferentially expressed IL-10-related genes. LM phi obtained from mice lacking IL-10 or Stat3 showed hyperproduction of tumour necrosis factor (TNF)-alpha and IL-6 in response to LPS. IL-10 production in the large intestine was mainly induced by LM phi and regulatory T cells and was dependent on the presence of commensal microbiota. Accordingly, LM phi from germ-free mice showed less production of IL-10 and increased levels of LPS-induced TNF-alpha and IL-6 production. Taken together, these results demonstrate that the activity of LM phi to produce pro-inflammatory cytokines is negatively regulated through commensal microbiota-dependent IL-10 production in the large intestine.