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MUC2 DEFICIENCY INTERFERED IN HOST DEFENSE IN ENTERIC PARASITE INFECTION
J-E Ghia1, H Wang1, N Haq1, Y Deng1, R El-Sharkawy1, A Velcich2, WI Khan1
1Intestinal Disease Research Program, Department of Medicine, McMaster University, Hamilton, Ontario; 2Department of Oncology, Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, NY, USA
BACKGROUND AND AIM: Goblet cells reside throughout the small and large intestine and are the main source of mucins in the gut. Hyperplasia of mucin secreting goblet cells accompany in a number of enteric infections including infections by nematode parasites. Nevertheless, the precise role of mucins in host defense in nematode infection remains to be determined. The aim of the present study was to investigate the role of mucin Muc2 in host protection in a model of nematode infection.
METHODS: Muc2 deficient (Muc2–/–) and their wild-type (Muc2+/+) mice were infected with nematode, Trichuris muris and euthanized post-infection (pi) to investigate worm expulsion, inflammatory parameters and cytokines.
RESULTS: Expulsion of worms from the intestine was significantly delayed in Muc2–/– mice as compared to Muc2+/+ mice (worm burden: 24.4±10.5 and 97.8±27.2 in Muc2–/– and Muc2+/+ mice, respectively on day 20 pi). Consistent with delayed worm expulsion, we also observed a marked impairment in the development of infection-induced intestinal goblet cell hyperplasia in Muc2 deficient mice. In spite of interference in worm expulsion, there was no significant difference in the production of Th2 cytokines (IL-4 and IL-13) in colonic tissues and from in vitro ConA stimulated spleen cells between Muc2+/+ and Muc2–/– mice following infection. Muc2 deficiency enhanced myeloperoxidase (MPO) activity but had no significant effect on IL-1beta production elicited by T. muris infection.
CONCLUSION: Taken together, the present study strongly suggests that Muc2 is an important component of innate host defense in enteric parasite infection and for the first time demonstrates an important contribution of this mucin gene in host protection in nematode infection.