Masuda Atsuhiro, Yoshida Masaru, Shiomi Hideyuki, Ikezawa Satoshi, Takagawa Tetsuya, Tanaka Hiroshi, Chinzei Ryo, Ishida Tsukasa, Morita Yoshinori, Kutsumi Hiromu, Inokuchi Hideto, Wang Shuo, Kobayashi Kanna, Mizuno Shigeto, Nakamura Akira, Takai Toshiyuki, Blumberg Richard S, Azuma Takeshi
Department of Gastroenterology, Kobe University School of Medicine, 7-5-1, Chu-o-ku, Kusunoki-Cho, Kobe, Hyogo 650-0017, Japan.
Infect Immun. 2008 Apr;76(4):1728-37. doi: 10.1128/IAI.01493-07. Epub 2008 Jan 28.
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 immunoglobulin 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 Fcgamma receptors (FcgammaRs), the receptors for the Fc portion of IgG, regulate this bacterial infection within mucosal tissues. Therefore, we investigated the roles of FcgammaRs during C. rodentium infection. Fc receptor common gamma chain (FcRgamma)-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 FcgammaRs, phagocytosis by macrophages was significantly diminished. Therefore, activating FcgammaRs 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.
鼠柠檬酸杆菌是肠道致病性大肠杆菌的一种小鼠模型病原体,它通过黏附与抹除性病变定殖于结肠,从而特异性地黏附于肠道上皮细胞表面并引发黏膜炎症。CD4+ T细胞、B细胞和免疫球蛋白G(IgG),而非分泌型IgA或IgM,在根除这种病原体中发挥关键作用。与IgG在根除鼠柠檬酸杆菌中的重要性相一致,肠道上皮细胞内的新生儿IgG Fc受体介导的IgG转运在调节鼠柠檬酸杆菌感染中也起着关键作用。然而,IgG的Fc段受体即Fcγ受体是否在黏膜组织内调节这种细菌感染仍有待确定。因此,我们研究了Fcγ受体在鼠柠檬酸杆菌感染过程中的作用。Fc受体共同γ链(FcRγ)缺陷小鼠对鼠柠檬酸杆菌诱导的结肠炎更易感。这是由于FcR介导的内吞作用以及树突状细胞成熟效率降低,进而导致抗原特异性T细胞的T细胞活化减少所致。此外,在缺乏Fcγ受体的情况下,巨噬细胞的吞噬作用显著减弱。因此,激活Fcγ受体在抵御鼠柠檬酸杆菌感染中发挥重要作用,这表明IgG在这种感染中所起的关键作用并非仅由IgG介导,而是依赖于这类受体。