Smith Philip, Mangan Niamh E, Walsh Caitriona M, Fallon Rosie E, McKenzie Andrew N J, van Rooijen Nico, Fallon Padraic G
Institute of Molecular Medicine, St. James's Hospital, Trinity College Dublin, Dublin 8, Ireland.
J Immunol. 2007 Apr 1;178(7):4557-66. doi: 10.4049/jimmunol.178.7.4557.
The propensity of a range of parasitic helminths to stimulate a Th2 or regulatory cell-biased response has been proposed to reduce the severity of experimental inflammatory bowel disease. We examined whether infection with Schistosoma mansoni, a trematode parasite, altered the susceptibility of mice to colitis induced by dextran sodium sulfate (DSS). Mice infected with schistosome worms were refractory to DSS-induced colitis. Egg-laying schistosome infections or injection of eggs did not render mice resistant to colitis induced by DSS. Schistosome worm infections prevent colitis by a novel mechanism dependent on macrophages, and not by simple modulation of Th2 responses, or via induction of regulatory CD4+ or CD25+ cells, IL-10, or TGF-beta. Infected mice had marked infiltration of macrophages (F4/80+CD11b+CD11c(-)) into the colon lamina propria and protection from DSS-induced colitis was shown to be macrophage dependent. Resistance from colitis was not due to alternatively activated macrophages. Transfer of colon lamina propria F4/80+ macrophages isolated from worm-infected mice induced significant protection from colitis in recipient mice treated with DSS. Therefore, we propose a new mechanism whereby a parasitic worm suppresses DSS-induced colitis via a novel colon-infiltrating macrophage population.
一系列寄生蠕虫刺激偏向Th2或调节性细胞反应的倾向已被提出可减轻实验性炎症性肠病的严重程度。我们研究了曼氏血吸虫(一种吸虫寄生虫)感染是否会改变小鼠对葡聚糖硫酸钠(DSS)诱导的结肠炎的易感性。感染血吸虫的小鼠对DSS诱导的结肠炎具有抗性。产卵的血吸虫感染或注射虫卵并不能使小鼠对DSS诱导的结肠炎产生抗性。血吸虫感染通过一种依赖巨噬细胞的新机制预防结肠炎,而不是通过简单调节Th2反应,或通过诱导调节性CD4+或CD25+细胞、IL-10或TGF-β。感染小鼠的结肠固有层有明显的巨噬细胞(F4/80+CD11b+CD11c(-))浸润,并且已表明对DSS诱导的结肠炎的保护作用依赖于巨噬细胞。对结肠炎的抗性并非由于替代性活化的巨噬细胞。从感染蠕虫的小鼠中分离出的结肠固有层F4/80+巨噬细胞转移到接受DSS治疗的受体小鼠中,可诱导对结肠炎的显著保护。因此,我们提出了一种新机制,即寄生蠕虫通过一种新的结肠浸润巨噬细胞群体抑制DSS诱导的结肠炎。