The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection

The role of Th2 cytokines, chemokines and parasite products in eosinophil recruitment to the gastrointestinal mucosa during helminth infection
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DOI:
10.1002/eji.200535492
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发表时间:
2006-07-01
影响因子:
5.4
通讯作者:
Else, Kathryn J.
Else, Kathryn J.
中科院分区:
医学3区
文献类型:
--
作者:
Dixon, Helen;Blanchard, Carine;Else, Kathryn J.

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被引文献

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旋毛虫和鼠鞭虫是小鼠的线虫寄生虫,分别寄生在小肠和大肠中:蠕虫驱逐需要Th 2免疫应答的发展。趋化因子CCL 11是趋化因子受体CCR 3的激动剂,并与IL-5协同作用以将嗜酸性粒细胞募集到炎症部位。CCL 11在胃肠道蠕虫感染中的作用以前没有研究过。我们用旋毛虫肌幼虫或鼠旋毛虫卵攻击野生型(WT)BALB/c、CCL 11单敲除(SKO)和CCL 11 IL-5双敲除(DKO)小鼠,以检查蠕虫感染期间嗜酸性粒细胞向小肠和大肠的募集。外周嗜酸性粒细胞增多症被认为是在WT和SKO小鼠在旋毛虫感染,但没有与鼠旋毛虫。胃肠道嗜酸性粒细胞显著减少,但在SKO小鼠中没有消融-在DKO小鼠中可以忽略不计-感染任一线虫。残留的嗜酸性粒细胞和上调的CCL 24 mRNA在胃肠道的SKO小鼠感染任一线虫,连同嗜酸性粒细胞活性因子的存在下,旋毛虫和鼠旋毛虫产品,表明CCL 11是突出的,但不是唯一的嗜酸性粒细胞化学引诱剂的生物学意义,在胃肠道蠕虫感染。
Trichinella spiralis and Trichuris muris are nematode parasites of the mouse, dwelling in the small and large intestines, respectively: worm expulsion requires development of a Th2 immune response. The chemokine CCL11 is agonist for the chemokine receptor CCR3 and acts in synergy with IL-5 to recruit eosinophils to inflammatory sites. The role of CCL11 in gastrointestinal helminth infection has not been previously studied. We challenged wild-type (WT) BALB/c, CCL11 single knockout (SKO) and CCL11 IL-5 double knockout (DKO) mice with either T spiralis muscle larvae or T muris eggs in order to examine eosinophil recruitment to the small and large intestine during helminth infection. A peripheral eosinophilia was seen in WT and SKO mice during T spiralis infection but not with T muris. Gastrointestinal eosinophilia was markedly reduced but not ablated in SKO mice - and negligible in DKO mice - infected with either nematode. The residual eosinophilia and up-regulation of CCL24 mRNA in the gastrointestinal tract of SKO mice infected with either nematode, together with the presence of an eosinophil-active factor in T spiralis and T muris products, suggest that CCL11 is the salient but not the sole eosinophil chemoattractant of biological significance during gastrointestinal helminth infection.