RRC ID 3169
著者 Shim DH, Suzuki T, Chang SY, Park SM, Sansonetti PJ, Sasakawa C, Kweon MN.
タイトル New animal model of shigellosis in the Guinea pig: its usefulness for protective efficacy studies.
ジャーナル J Immunol
Abstract 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 approximately 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-1beta, 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.
巻・号 178(4)
ページ 2476-82
公開日 2007-2-15
DOI 10.4049/jimmunol.178.4.2476
PII 178/4/2476
PMID 17277155
MeSH Acute Disease Animals Colon / immunology* Colon / pathology Dysentery, Bacillary / immunology* Dysentery, Bacillary / pathology Dysentery, Bacillary / prevention & control Female Gene Expression Regulation / immunology Guinea Pigs Immunoglobulin A / immunology Inflammation / immunology Inflammation / pathology Interleukin-1beta / immunology Interleukin-8 / immunology Models, Animal Nitric Oxide Synthase / immunology Proctocolitis / immunology* Proctocolitis / pathology Proctocolitis / prevention & control Shigella Vaccines / immunology* Shigella Vaccines / pharmacology Shigella flexneri / immunology* Vaccines, Attenuated / immunology* Vaccines, Attenuated / pharmacology
IF 4.886
引用数 66
WOS 分野 IMMUNOLOGY
リソース情報
病原微生物