Lack of host gut microbiota alters immune responses and intestinal granuloma formation during schistosomiasis
Lack of host gut microbiota alters immune responses and intestinal granuloma formation during schistosomiasis
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DOI：
10.1111/cei.12230
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发表时间：
2014-02-01
影响因子：
4.6
通讯作者：
da Costa, C. Prazeres
中科院分区：
文献类型：
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作者：
Holzscheiter, M.;Layland, L. E.;da Costa, C. Prazeres
寄生虫感染的死亡是由于肉芽肿性免疫介导的对被困在宿主组织中的卵的反应。血吸虫特异性免疫应答的特征在于初始的辅助性T细胞1型（Th1）应答，并且我们先前的研究表明，髓样分化初级应答基因88（Myd 88）缺陷小鼠未能在体内启动这种应答。特异性地，溶酶体抗原在体外不能刺激先天细胞释放促炎细胞因子。由于曼氏血吸虫感染是一种肠道疾病，我们假设肠道细菌可以作为肠道先天免疫系统的旁观者激活剂，以激发Th1应答。使用广泛的口服抗生素和抗真菌药，我们分析了同时耗尽肠道细菌的寄生虫感染小鼠。消耗后，肠道炎症明显减少，同时肠道肉芽肿的发展也减少。相反，肝脏病理学保持不变。此外，寄生虫体特异性免疫反应发生偏斜，粪便虫卵排泄减少。这项研究表明，宿主微生物群可以作为第三伙伴，激发蠕虫特异性免疫反应。
Fatalities from schistosome infections arise due to granulomatous, immune-mediated responses to eggs that become trapped in host tissues. Schistosome-specific immune responses are characterized by initial T helper type 1 (Th1) responses and our previous studies demonstrated that myeloid differentiation primary response gene 88 (Myd88)-deficient mice failed to initiate such responses in vivo. Paradoxically, schistosomal antigens fail to stimulate innate cells to release proinflammatory cytokines in vitro. Since Schistosomamansoni infection is an intestinal disease, we hypothesized that commensal bacteria could act as bystander activators of the intestinal innate immune system to instigate Th1 responses. Using a broad spectrum of orally administered antibiotics and anti-mycotics we analysed schistosome-infected mice that were simultaneously depleted of gut bacteria. After depletion there was significantly less inflammation in the intestine, which was accompanied by decreased intestinal granuloma development. In contrast, liver pathology remained unaltered. In addition, schistosome-specific immune responses were skewed and faecal egg excretion was diminished. This study demonstrates that host microbiota can act as a third partner in instigating helminth-specific immune responses.