| First Author | Kissoon-Singh V | Year | 2013 |
| Journal | Am J Pathol | Volume | 182 |
| Issue | 3 | Pages | 852-65 |
| PubMed ID | 23357502 | Mgi Jnum | J:317084 |
| Mgi Id | MGI:6843375 | Doi | 10.1016/j.ajpath.2012.11.035 |
| Citation | Kissoon-Singh V, et al. (2013) Entamoeba histolytica exacerbates epithelial tight junction permeability and proinflammatory responses in Muc2(-/-) mice. Am J Pathol 182(3):852-65 |
| abstractText | Human mucin-2 (MUC-2) is the first line of innate host defense in preventing pathogen-induced epithelial injury. Entamoeba histolytica (Eh) colonizes the mucus layer by binding of the parasite's surface galactose lectin to galactose and N-acetyl-d-galactosamine residues on colonic MUC-2, preventing parasite contact-dependent cytolysis of epithelial cells. We quantified early innate responses to Eh in wild-type and MUC-2-deficient mice (Muc2(-/-)) using closed colonic loops. Eh infection in wild-type but not Muc2(-/-) mice induced a time-dependent increase in (3)H-labeled mucin and nonmucin glycoprotein secretions. Immunohistochemical staining revealed intense MUC-2 secretion, which formed a thick, protective mucus plug overlying the surface epithelium, entrapping Eh. In Muc2(-/-) mice, Eh induced a pronounced time-dependent secretory exudate with increased gross pathology scores and serum albumin leakage. Colonic pathology, secretory responses, and increased proinflammatory cytokine secretions of TNF-alpha, IFN-gamma, and IL-13 correlated with altered expression of the tight junction proteins claudin-2, occludin, and ZO-1. We identified the putative Eh virulence factor that elicits the proinflammatory responses and alters tight junction permeability as Eh cysteine protease A5 (EhCP-A5). The present findings demonstrate that colonic mucins confer both luminal and epithelial barrier functions and that, in the absence of MUC-2, mice are more susceptible to Eh-induced secretory and proinflammatory responses mediated by EhCP-A5. |
