title: A mouse model of shigellosis by intraperitoneal infection.
abstract: In human and nonhuman primates, Shigella spp. cause bacillary dysentery by invading colon epithelium and promoting a strong inflammatory response; however, adult mice are resistant to oral Shigella infection. In this study, intraperitoneal challenge with virulent S. flexneri 2a (YSH6000) resulted in diarrhea and severe body weight loss in adult B6 mice. Of note, virulent S. flexneri 2a could invade and colonize not only systemic tissues but also the serosa and lamina propria region of the large intestine. In addition, epithelial shedding, barrier integrity, and goblet cell hyperplasia were found in the large intestine by 24 hours post-intraperitoneal Shigella infection. Of note, predominant expression of proinflammatory cytokines and chemokines were found in the large intestine after intraperitoneal challenge. Monocytes played a critical role in attenuating diarrhea and in providing protective efficacy against intraperitoneal Shigella infection. Most importantly, mice prevaccinated with attenuated S. flexneri 2a (SC602) strain were protected against intraperitoneal challenge with YSH6000. When taken together, these findings show that intraperitoneal challenge with virulent S. flexneri 2a can provoke bacillary dysentery and severe pathogenesis in adult mice. This model may be helpful for understanding the induction mechanism of bacillary dysentery and for evaluating Shigella vaccine candidates.
authors.affiliation: Mucosal Immunology Section, International Vaccine Institute, Seoul.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Yang
authors.forename: Se-Na
authors.initials: SN
authors.lastname: Lee
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Chang
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Ko
authors.forename: Sangryeol
authors.initials: S
authors.lastname: Ryu
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
mesh_terms: D000825:Animal Structures / Q000382:microbiology / Q000473:pathology; D000818:Animals; D001835:Body Weight; D016207:Cytokines / Q000032:analysis; D003967:Diarrhea / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D004405:Dysentery, Bacillary / Q000382:microbiology / Q000473:pathology*; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012763:Shigella flexneri / Q000254:growth & development*; D016019:Survival Analysis
chemical_list: D016207:Cytokines
keywords: CCR2+ monocytes; S. flexneri; intraperitoneal route; mouse model; shigellosis