Muc5ac: a critical component mediating the rejection of enteric nematodes

被引:226
作者
Hasnain, Sumaira Z. [1 ,2 ]
Evans, Christopher M. [3 ]
Roy, Michelle [3 ]
Gallagher, Amanda L. [2 ]
Kindrachuk, Kristen N. [4 ]
Barron, Luke [4 ]
Dickey, Burton F. [3 ]
Wilson, Mark S. [5 ]
Wynn, Thomas A. [4 ]
Grencis, Richard K. [2 ]
Thornton, David J. [1 ]
机构
[1] Univ Manchester, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England
[2] Univ Manchester, Manchester Immunol Grp, Fac Life Sci, Manchester M13 9PT, Lancs, England
[3] Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA
[4] NIAID, Immunopathogenesis Sect, NIH, Bethesda, MD 20892 USA
[5] Natl Inst Med Res, Div Mol Immunol, Med Res Council, London NW7 1AA, England
基金
美国国家卫生研究院; 英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
MUCIN GENE-EXPRESSION; ABNORMAL EXPRESSION; MUCUS; INFECTIONS; BARRIER; ALPHA; COLON; MICE;
D O I
10.1084/jem.20102057
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
De novo expression of Muc5ac, a mucin not normally expressed in the intestinal tract, is induced in the cecum of mice resistant to Trichuris muris infection. In this study, we investigated the role of Muc5ac, which is detected shortly before worm expulsion and is associated with the production of interleukin-13 (IL-13), in resistance to this nematode. Muc5ac-deficient mice were incapable of expelling T. muris from the intestine and harbored long-term chronic infections, despite developing strong T(H)2 responses. Muc5ac-deficient mice had elevated levels of IL-13 and, surprisingly, an increase in the T(H)1 cytokine IFN-gamma. Because T(H)1 inflammation is thought to favor chronic nematode infection, IFN-gamma was neutralized in vivo, resulting in an even stronger T(H)2-type immune response. Nevertheless, despite a more robust T(H)2 effector response, the Muc5ac-deficient mice remained highly susceptible to chronic T. muris infection. Importantly, human MUC5AC had a direct detrimental effect on nematode vitality. Moreover, the absence of Muc5ac caused a significant delay in the expulsion of two other gut-dwelling nematodes (Trichinella spiralis and Nippostrongylus brasiliensis). Thus, for the first time, we identify a single mucin, Muc5ac, as a direct and critical mediator of resistance during intestinal nematode infection.
引用
收藏
页码:893 / 900
页数:8
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