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* Mucosal Immunology Section, International Vaccine Institute, Seoul, Korea;
Division of Bacterial Pathogenesis, Department of Microbiology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan;
Unité de Pathogénie, Microbienne Moléculaire, Unité 786, Institut National de la Santé et de la Recherche Médicale and Howard Hughes Medical Institute, Institut Pasteur, Paris, France; and
Division of Microbiology and Immunology, Department of Infectious Diseases Control, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Tokyo, Japan
It has been difficult to evaluate the protective efficacy of vaccine candidates against shigellosis, a major form of bacillary dysentery caused by Shigella spp. infection, because of the lack of suitable animal models. To develop a proper animal model representing human bacillary dysentery, guinea pigs were challenged with virulent Shigella flexneri serotype 2a (strains 2457T or YSH6000) or S. flexneri 5a (strain M90T) by the intrarectal (i.r.) route. Interestingly, all guinea pigs administered these Shigella strains developed severe and acute rectocolitis. They lost 
20% of their body weight and developed tenesmus by 24 h after Shigella infection. Shigella invasion and colonization of the distal colon were seen at 24 h but disappeared by 48 h following i.r. infection. Histopathological approaches demonstrated significant damage and destruction of mucosal and submucosal layers, thickened intestinal wall, edema, erosion, infiltration of neutrophils, and depletion of goblet cells in the distal colon. Furthermore, robust expression of IL-8, IL-1
, and inducible NO synthase mRNA was detected in the colon from 6 to 24 h following Shigella infection. Most importantly, in our new shigellosis model, guinea pigs vaccinated with an attenuated S. flexneri 2a SC602 strain possessing high levels of mucosal IgA Abs showed milder symptoms of bacillary dysentery than did animals receiving PBS alone after Shigella infection. In the guinea pig, administration of Shigella by i.r. route induces acute inflammation, making this animal model useful for assessing the protective efficacy of Shigella vaccine candidates.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work is supported by the governments of the Republic of Korea, Sweden, and Kuwait, by Science Research Center funds to the Immunomodulation Research Center at the University of Ulsan from the Korean Science and Engineering Foundation and the Korean Ministry of Science and Technology, and by Grant RT104-01-01 from the Regional Technology Innovation Program, Ministry of Commerce, Industry and Energy, by Japan Science and Technology Agency, and Grant-in-Aid for Scientific Research from Japanese Ministry of Education, Culture, Sports and Technology, and by the Naito Foundation and Takeda Science Foundation.
2 Address correspondence and reprint requests to Dr. Mi-Na Kweon, Mucosal Immunology Section, International Vaccine Institute, Seoul National University Research Park, Kwanak-Gu, Seoul 151-818, Korea. E-mail address: mnkweon{at}ivi.int
3 Abbreviations used in this paper: PMN, polymorphonuclear cell; i.r., intrarectal; PAS, periodic acid-Schiff; iNOS, inducible NO synthase.
4 The online version of this article contains supplemental material.
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