IFN-inducible p47 GTPases display differential responses to Schistosoma japonicum acute infection
IFN-inducible p47 GTPases display differential responses to Schistosoma japonicum acute infection
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IFN诱导的p47 GTP酶对日本血吸虫急性感染表现出不同的反应
DOI：
10.1038/cmi.2009.100
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发表时间：
2010-01-01
影响因子：
24.1
通讯作者：
Wu, Guanling
中科院分区：
文献类型：
--
作者：
Chen, Xuesong;Du, Xiaotang;Wu, Guanling
干扰素γ诱导的GTP酶（也称为Irgm 3）和干扰素γ诱导的蛋白47（IRG-47）（也称为Irgd）是干扰素（IFN）诱导的p47 GTP酶，已显示其调节宿主对细胞内病原体的抗性。关于p47 GTP酶在宿主对细胞外病原体的应答中的作用知之甚少。为探讨IGTP和IRG-47在日本血吸虫感染过程中的作用，用日本血吸虫尾蚴攻击IGTP和IRG-47基因敲除小鼠和野生型小鼠。japonicum，并分析了宿主反应。在S.日本血吸虫感染后，缺乏IGTP的小鼠表现出与WT小鼠相似的寄生虫负荷和病理损伤。重要的是，S.与IGTP缺陷型小鼠和WT小鼠相比，日本血吸虫感染的IRG-47缺陷型小鼠表现出显著减少的蠕虫和较低的虫卵负荷，但在肝叶的外周部分中由虫卵引起的强烈的肉芽肿反应。此外，使用寡核苷酸微阵列在IRG-47缺陷小鼠的脾脏中观察到炎症相关基因表达的上调，其中突出显示了精氨酸-细胞因子受体相互作用、T细胞受体信号传导、补体、凝血级联和细胞粘附分子的多种途径。综上所述，这些数据表明，IGTP和IRG-47可能具有不同的特征，这些特征是抵抗S的差异所需的。山茱萸
Interferon gamma induced GTPase (IGTP)(also named Irgm3) and interferon gamma inducible protein 47 (IRG-47)(also named Irgd) are interferon (IFN)-inducible p47 GTPases that have been shown to regulate host resistance to intracellular pathogens. Little knowledge has been known about the role of p47 GTPases in host responses against extracellular pathogens. To investigate possible roles of IGTP and IRG-47 in the course of Schistosoma japonicum infection, IGTP and IRG-47 knockout and wild-type (WT) mice were challenged with cercariae of S. japonicum, and host responses were analyzed. At the acute stage of S. japonicum infection, mice that lacked IGTP displayed similar parasite burden and pathological damage to WT mice. Importantly, S. japonicum-infected IRG-47-deficient mice, in contrast to IGTP-deficient mice and WT mice, showed significantly reduced worms and lower egg-burden, but intense granulomatous reaction evoked by schistosome eggs in peripheral parts of liver lobes. In addition, upregulation of inflammation-related gene expression was observed in the spleen of IRG-47-deficient mice using oligonucleotide microarrays, in which multiple pathways of cytokine–cytokine receptor interaction, T-cell receptor signaling, complement, coagulation cascades and cell adhesion molecules were highlighted. Taken together, these data suggest that IGTP and IRG-47 might have distinct features that were differentially required for resistance to S. japonicum.