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Infection and Immunity, March 2008, p. 927-934, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01145-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Peyer's Patches Are Required for Intestinal Immunoglobulin A Responses to Salmonella spp.{triangledown}

Tomomi Hashizume,1 Atsushi Togawa,2 Tomonori Nochi,3 Osamu Igarashi,3 Mi-Na Kweon,4 Hiroshi Kiyono,3 and Masafumi Yamamoto1*

Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, Chiba, Japan,1 Laboratory for Stem Cell Biology, RIKEN Center for Developmental Biology, Hyogo, Japan,2 Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo, Japan,3 Mucosal Immunology Section, International Vaccine Institute, Seoul, Korea4

Received 18 August 2007/ Returned for modification 10 September 2007/ Accepted 3 December 2007

Previous studies have shown that Peyer's patches (PP) are not required for intestinal immunoglobulin A (IgA) responses to orally administered soluble protein. However, the roles of PP in regulation of mucosal immune responses against bacterial antigen remain to be clarified. In the present study, we generated several gut-associated lymphoreticular tissue-null mice by treatment with anti-interleukin-7 receptor antibody, the fusion protein of lymphotoxin β receptor and IgG Fc, and/or tumor necrosis factor receptor p55 and IgG Fc. These mice were then immunized with recombinant Salmonella expressing the C fragment of the tetanus toxin (rSalmonella-Tox C). Orally immunized PP-null mice as well as isolated lymphoid follicle (ILF)-null, PP/ILF-null, and PP/ILF/mesenteric lymph node-null mice induced identical levels of tetanus toxoid (TT)-specific systemic IgG responses to those of control mice. However, PP-null mice, but not ILF-null mice, failed to induce TT-specific intestinal IgA antibodies. Analysis of TT-specific CD4+ T-cell responses showed a reduction of gamma interferon (IFN-{gamma}) synthesis in the intestinal lamina propriae of PP-null mice given oral rSalmonella-Tox C. In contrast, TT-specific IFN-{gamma} responses in the spleen and delayed-type hypersensitivity responses were intact in those immunized mice. Interestingly, Salmonella lipopolysaccharide (LPS)-specific fecal IgA responses were not elicited in PP-null mice, while serum IgG anti-LPS antibodies were identical to those of control mice. These results suggest that while none of the gut-associated lymphoreticular tissues are required for the induction of systemic immune responses, PP are an essential lymphoid tissue for induction and regulation of intestinal IgA immunity against orally administered rSalmonella.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho-Nishi, Matsudo, Chiba 271-8587, Japan. Phone: 81-47-360-9336. Fax: 81-47-360-9601. E-mail: yamamoto.masafumi{at}nihon-u.ac.jp

{triangledown} Published ahead of print on 17 December 2007.

Editor: B. A. McCormick


Infection and Immunity, March 2008, p. 927-934, Vol. 76, No. 3
0019-9567/08/$08.00+0     doi:10.1128/IAI.01145-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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