Fcγ receptor regulation of Citrobacter rodentium infection
Fcγ receptor regulation of Citrobacter rodentium infection
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DOI：
10.1128/iai.01493-07
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发表时间：
2008-04-01
影响因子：
3.1
通讯作者：
Azuma, Takeshi
中科院分区：
文献类型：
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作者：
Masuda, Atsuhiro;Yoshida, Masaru;Azuma, Takeshi
鼠柠檬酸杆菌（Citrobacter rodentium）是肠道致病性大肠杆菌（Escherichia coli）的小鼠模型病原体，它利用附着和消退病变特异性地附着在肠上皮细胞表面并引起粘膜炎症，在结肠中定植。CD4(+) T细胞、B细胞和免疫球蛋白G (IgG)，而不是分泌IgA或IgM，在根除这种病原体中起关键作用。与IgG在啮齿鼠根除中的重要性一致，新生儿Fc受体在肠上皮内转运IgG为IgG在啮齿鼠感染的调节中也起着关键作用。然而，IgG Fc部分的受体Fc γ受体（Fc γ Rs）是否在粘膜组织内调节这种细菌感染仍有待确定。因此，我们研究了Fc γ Rs在啮齿鼠感染中的作用。铁受体γ链（FcR γ）缺陷小鼠更容易发生C.啮齿动物诱导的结肠炎。这是通过降低fcr介导的内吞作用和树突状细胞成熟的效率以及抗原特异性T细胞的T细胞活化而发生的。此外，在缺乏Fc γ Rs的情况下，巨噬细胞的吞噬作用明显减弱。因此，激活Fc γ Rs在防御啮齿鼠感染中发挥重要作用，这表明IgG在这种感染中发挥的关键作用不是IgG单独介导的，而是依赖于这类受体。
Citrobacter rodentium, a murine model pathogen for enteropathogenic Escherichia coli, colonizes the colon utilizing attaching and effacing lesions to adhere specifically to the surfaces of intestinal epithelial cells and cause mucosal inflammation. CD4(+) T cells, B cells, and immumoglobulin G (IgG), but not secretory IgA or IgM, play a critical role in eradicating this pathogen. Consistent with the importance of IgG in C. rodentium eradication, IgG transport by the neonatal Fc receptor for IgG within the intestinal epithelium also has a critical role in the regulation of C. rodentium infection. It remains to be determined, however, whether Fc gamma receptors (Fc gamma Rs), the receptors for the Fc portion of IgG, regulate this bacterial infection within mucosal tissues. Therefore, we investigated the roles of Fc gamma Rs during C. rodentium infection. Fe receptor common gamma chain (FcR gamma)-deficient mice were more susceptible to C. rodentium-induced colitis. This occurred through decreased efficiency of FcR-mediated endocytosis and maturation of dendritic cells and consequently T-cell activation of antigen-specific T cells. Moreover, in the absence of Fc gamma Rs, phagocytosis by macrophages was significantly diminished. Therefore, activating Fc gamma Rs play an important role in defending against C. rodentium infection, indicating that the critical role played by IgG in this infection is not mediated by IgG alone but is dependent upon this class of receptors.