Transfer of CD11c+ lamina propria mononuclear phagocytes from post-infectious irritable bowel syndrome causes mucosal barrier dysfunction and visceral hypersensitivity in recipient mice

Abstract

The role of low-grade inflammation in the development of post‑infectious irritable bowel syndrome (PI‑IBS) has attracted increasing attention. Abnormal CD11c+ mononuclear phagocytes, such as dendritic cells (DCs), macrophages, and monocytes, are involved in the disruption of immune tolerance in organisms, which can lead to the development of chronic inflammatory diseases. The present study tested the hypothesis that CD11c+ lamina propria mononuclear phagocytes (CD11c+ LPMPs) contribute to increased mucosal permeability and visceral hypersensitivity in a PI‑IBS mouse model. CD11c+ LPMPs were isolated and purified via the digestion of intestinal tissues and magnetic‑activated cell sorting. We detected increased mucosal permeability, visceral hypersensitivity and intestinal inflammation during both the acute and chronic stages of Trichinella infection. Following the transfer of CD11c+ LPMPs from PI‑IBS mice into normal mice, low‑grade inflammation was detected, as demonstrated by increased IL‑4 expression in the ileum, as well as enhanced mucosal permeability, as indicated by decreased transepithelial electrical resistance and the pre-sence of ultrastructural alterations. More importantly, the mice that underwent adoptive transfer of CD11c+ LPMPs from the PI‑IBS mice also exhibited increased abdominal withdrawal reflex scores and a decreased threshold. Our data demonstrated that the CD11c+ LPMPs from this PI‑IBS mouse model were not only able to transfer enteric inflammation to the normal mice but also caused abnormal intestinal function, characterized by epithelial barrier disruption and visceral hyperalgesia.

Mitochondrial translocator protein deficiency exacerbates pathology in acute experimental ulcerative colitis

“…Earlier up-regulation of Cd11c in Tspo −/− animals may reflect and/or influence the rapid onset and severity of colonic inflammation. In addition, CD11c + phagocytes may also increase gut mucosal epithelial permeability (Ren et al, 2017), further contributing to colonic pathology through increased bacterial translocation across the gut barrier. The upregulation of baseline colonic Cdx2 expression in Tspo −/− mice indicates that TSPO deficiency contributed to a homeostatic shift, perhaps compensating for decreased epithelial barrier function.…”

Thrombospondin-1 aggravates colonic mucosal inflammatory injuries via promoting the differentiation of CD11c+ macrophages with lysosomal activity limited in colitis

“…Lamina propria mononuclear cells (LPMC) and CD11c + lamina propria macrophages (CD11c + LPMP) were isolated and cultured as previously described (27,28). Colonic mucosal epithelial cells (cmECs) and colonic mucosal micro-vascular endothelial cells (cmVEC) were also isolated as described in previous studies (29,30).…”