Mucin gene deficiency in mice impairs host resistance to an enteric parasitic infection.

Mucin gene deficiency in mice impairs host resistance to an enteric parasitic infection.
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小鼠粘蛋白基因缺陷会损害宿主对肠道寄生虫感染的抵抗力。

DOI:
10.1053/j.gastro.2010.01.045
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发表时间:
2010-05
期刊:
影响因子:
29.4
通讯作者:
Khan WI
Khan WI
中科院分区:
医学1区
文献类型:
--
作者:
Hasnain SZ;Wang H;Ghia JE;Haq N;Deng Y;Velcich A;Grencis RK;Thornton DJ;Khan WI

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分泌粘蛋白的肠杯状细胞的增生伴随许多肠道感染,包括线虫寄生虫感染。然而,粘蛋白在线虫感染的宿主防御中的确切作用尚不清楚。我们研究了粘蛋白(Muc 2)在线虫感染模型中的蠕虫驱逐和宿主免疫中的作用。抗性(BALB/c,C57 BL/6),敏感(AKR),和Muc 2缺陷型小鼠品系感染线虫,鞭虫,蠕虫驱逐,鞭虫的能量状态,粘液/粘蛋白的变化,感染后的炎症和免疫反应进行了研究。Muc 2产生的增加,仅在耐药小鼠中观察到,与蠕虫排出相关。此外,在Muc 2缺陷小鼠中,蠕虫从肠道中排出的时间显著延迟。虽然在Muc 2缺陷小鼠中观察到过碘酸希夫(PAS)染色的肠杯状细胞的发育明显受损,但随着感染的进展,在这些小鼠中观察到PAS阳性杯状细胞的数量显著增加。令人惊讶的是,Muc 5ac(一种通常在气道和胃中表达的粘蛋白)在仅感染耐药动物后观察到增加。总的来说,耐药小鼠的粘液屏障比易感小鼠的粘液屏障渗透性更低。此外,从抗性小鼠中分离出的蠕虫具有较低的能量状态。粘蛋白是肠道感染先天防御的重要组成部分,这是第一次证明粘蛋白的重要功能,以保护宿主免受线虫感染。
Hyperplasia of mucin-secreting intestinal goblet cells accompanies a number of enteric infections, including infections by nematode parasites. Nevertheless, the precise role of mucins in host defense in nematode infection is not known. We investigated the role of the mucin (Muc2) in worm expulsion and host immunity in a model of nematode infection. Resistant (BALB/c, C57BL/6), susceptible (AKR), and Muc2-deficient mouse strains were infected with the nematode, Trichuris muris, and worm expulsion, energy status of the whipworms, changes in mucus/mucins, and inflammatory and immune responses were investigated after infection. The increase in Muc2 production, observed exclusively in resistant mice, correlated with worm expulsion. Moreover, expulsion of the worms from the intestine was significantly delayed in the Muc2-deficient mice. Although a marked impairment in the development of periodic acid Schiff (PAS)–stained intestinal goblet cells was observed in Muc2-deficient mice, as infection progressed a significant increase in the number of PAS-positive goblet cells was observed in these mice. Surprisingly, an increase in Muc5ac, a mucin normally expressed in the airways and stomach, was observed after infection of only the resistant animals. Overall, the mucus barrier in the resistant mice was less permeable than that of susceptible mice. Furthermore, the worms isolated from the resistant mice had a lower energy status. Mucins are an important component of innate defense in enteric infection; this is the first demonstration of the important functional contribution of mucins to host protection from nematode infection.
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