Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria
Masaru Yoshida, Kanna Kobayashi, Timothy T. Kuo, Lynn Bry, Jonathan N. Glickman, Steven M. Claypool, Arthur Kaser, Takashi Nagaishi, Darren E. Higgins, Emiko Mizoguchi, Yoshio Wakatsuki, Derry C. Roopenian, Atsushi Mizoguchi, Wayne I. Lencer, Richard S. Blumberg
Masaru Yoshida, Kanna Kobayashi, Timothy T. Kuo, Lynn Bry, Jonathan N. Glickman, Steven M. Claypool, Arthur Kaser, Takashi Nagaishi, Darren E. Higgins, Emiko Mizoguchi, Yoshio Wakatsuki, Derry C. Roopenian, Atsushi Mizoguchi, Wayne I. Lencer, Richard S. Blumberg
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Research Article Gastroenterology

Neonatal Fc receptor for IgG regulates mucosal immune responses to luminal bacteria

Abstract

The neonatal Fc receptor for IgG (FcRn) plays a major role in regulating host IgG levels and transporting IgG and associated antigens across polarized epithelial barriers. Selective expression of FcRn in the epithelium is shown here to be associated with secretion of IgG into the lumen that allows for defense against an epithelium-associated pathogen (Citrobacter rodentium). This pathway of host resistance to a bacterial pathogen as mediated by FcRn involves retrieval of bacterial antigens from the lumen and initiation of adaptive immune responses in regional lymphoid structures. Epithelial-associated FcRn, through its ability to secrete and absorb IgG, may thus integrate luminal antigen encounters with systemic immune compartments and as such provide essential host defense and immunoregulatory functions at the mucosal surfaces.

Authors

Masaru Yoshida, Kanna Kobayashi, Timothy T. Kuo, Lynn Bry, Jonathan N. Glickman, Steven M. Claypool, Arthur Kaser, Takashi Nagaishi, Darren E. Higgins, Emiko Mizoguchi, Yoshio Wakatsuki, Derry C. Roopenian, Atsushi Mizoguchi, Wayne I. Lencer, Richard S. Blumberg

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Figure 3

Susceptibility toC. rodentium infection in the presence of FcRn.

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Susceptibility toC. rodentium infec...
(A and B) Susceptibility to infection with 1 × 109 CFU of C. rodentium in FcRn–/– BALB/c mice. (A) Body weight changes in FcRn–/– and FcRn+/– mice with C. rodentium infection. (B) CFU of C. rodentium in feces of FcRn–/– and FcRn+/– mice 21 days after infection. Mean ± SD are shown for each group (n = 6). (C–E) Susceptibility to infection with C. rodentium in FcRn–/– C57BL/6 mice. Survival rate (C) and body weight changes (D) in FcRn–/– and FcRn+/– mice with C. rodentium infection. (E) CFU of C. rodentium in feces of FcRn–/– and FcRn–/+ mice 21 days after infection. Mean ± SD are shown for each group (n = 8). (F) Immunohistochemical analysis of the colon to detect intimin in mice with C. rodentium infection. Colonic tissues were collected at day 7 from selected mice on a C57BL/6 background. Sections were stained for intimin using a polyclonal rabbit anti–C. rodentium intimin antibody (red) and nuclei (blue) and were examined by confocal microscopy. Magnification, ×400. Macroscopic findings (G) and the length of colon (H) in FcRn–/– and FcRn+/– C57BL/6 mice, uninfected or infected with C. rodentium, at 21 days after infection. (I) Histological findings of colon in FcRn–/– and littermate FcRn+/– C57BL/6 mice with or without C. rodentium infection (21 days after infection). Magnification, ×100. (J) Histological score of colonic tissue in the mice with or without C. rodentium infection at day 21. *P < 0.05.