Tissue Eosinophilia in a Mouse Model of Colitis Is Highly Dependent on TLR2 and Independent of Mast Cells

Abstract

The mechanisms initiating eosinophil influx into sites of inflammation have been well studied in allergic disease but are poorly understood in other settings. This study examined the roles of TLR2 and mast cells in eosinophil accumulation during a nonallergic model of eosinophilia-associated colitis. TLR2-deficient mice (TLR2 ؊/؊ ) developed a more severe colitis than wild-type mice in the dextran sodium sulfate (DSS) model. However, they had significantly fewer eosinophils in the submucosa of the cecum (P < 0.01) and mid-colon (P < 0.01) than did wild-type mice after DSS treatment. Decreased eosinophilia in TLR2 ؊/؊ mice was associated with lower levels of cecal CCL11 (P < 0.01). Peritoneal eosinophils did not express TLR2 protein, but TLR2 ligand injection into the peritoneal cavity induced local eosinophil recruitment, indicating that TLR2 activation of other cell types can mediate eosinophil recruitment. After DSS treatment, mast celldeficient (Kit W-sh/W-sh ) mice had similar levels of intestinal tissue eosinophilia were observed as those in wild-type mice. However, mast cell-deficient mice were partially protected from DSS-induced weight loss, an effect that was reversed by mast cell reconstitution. Overall, this study indicates a critical role for indirect TLR2-dependent pathways, but not mast cells, in the generation of eosinophilia in the large intestine during experimental colitis and has important implications for the regulation of eosinophils at mucosal inflammatory sites.

Dietary Chitin Particles Called Mimetic Fungi Ameliorate Colitis in Toll-Like Receptor 2/CD14- and Sex-Dependent Manners

“…Previously, we identified that TLR2 and CD14 are essential for CMP-induced classical macrophage (M1) activation of peritoneal macrophages (29). TLR2 KO and CD14 KO mice are known to develop more severe colitis than wild-type (WT) mice in response to DSS treatments, indicating that both TLR2 and CD14 play protective roles (41,42). Therefore, we used 3%, instead of 4%, DSS and explored whether these chitin-binding proteins were responsible for anti-inflammatory effects of LCBs using male mice deficient in TLR2 and male mice deficient in CD14.…”

Escherichia coli strain Nissle 1917 ameliorates experimental colitis by modulating intestinal permeability, the inflammatory response and clinical signs in a faecal transplantation model

“…They are recruited by chemokines that act on CCR3, especially eotaxin, and are able to secrete toxic inflammatory mediators, such as EPO, which is stored within vesicles (Al-Haddad & Riddell, 2005;Woodruff et al, 2011). Eosinophils are thought to play a major pro-inflammatory role in IBD and contribute to diarrhoea, tissue destruction and fibrosis formation (Vieira et al, 2009;Albert et al, 2011). It has recently been suggested that eosinophils may also contribute to tissue repair during IBD (Travers & Rothenberg, 2015).…”

In VivoPhysiological and Transcriptional Profiling Reveals Host Responses to Clostridium difficile Toxin A and Toxin B

“…Each of these five parameters was scored between zero and three, yielding total pathology scores between zero and fifteen. Eosinophils were detected in tissue using Congo red staining (39). Tissues for H&E, myeloperoxidase (MPO), and eosinophil staining were fixed in Bouin's solution; tissues for other measurements were fixed in 4% paraformaldehyde.…”