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Infection and Immunity, April 2008, p. 1728-1737, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01493-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Fc{gamma} Receptor Regulation of Citrobacter rodentium Infection{triangledown}

Atsuhiro Masuda,1 Masaru Yoshida,1* Hideyuki Shiomi,1 Satoshi Ikezawa,1 Tetsuya Takagawa,1 Hiroshi Tanaka,1 Ryo Chinzei,1 Tsukasa Ishida,1 Yoshinori Morita,1 Hiromu Kutsumi,1 Hideto Inokuchi,1 Shuo Wang,3 Kanna Kobayashi,3 Shigeto Mizuno,4 Akira Nakamura,2 Toshiyuki Takai,2 Richard S. Blumberg,3 and Takeshi Azuma1

Department of Gastroenterology, Kobe University School of Medicine, Kobe, Hyogo,1 Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan,2 Gastroenterology Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts,3 Department of Medical Pharmaceutics, Kobe Pharmaceutical University, Kobe, Hyogo, Japan4

Received 8 November 2007/ Returned for modification 13 December 2007/ Accepted 20 January 2008

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 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. Fc 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.

* Corresponding author. Mailing address: Department of Gastroenterology, Kobe University School of Medicine, 7-5-1, Chu-o-ku, Kusunoki-Cho, Kobe, Hyogo 650-0017, Japan. Phone: 81-78-382-6305. Fax: 81-78-382-6309. E-mail: myoshida{at}med.kobe-u.ac.jp

{triangledown} Published ahead of print on 28 January 2008.

Editor: S. R. Blanke

Infection and Immunity, April 2008, p. 1728-1737, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01493-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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