Mucosal Immunology Section, International Vaccine Institute, Seoul.
J Infect Dis. 2014 Jan 15;209(2):203-15. doi: 10.1093/infdis/jit399. Epub 2013 Jul 31.
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.
在人类和非人类灵长类动物中，志贺氏菌属通过侵袭结肠上皮并促进强烈的炎症反应引起细菌性痢疾；然而，成年小鼠对口服志贺氏菌感染具有抗性。在本研究中，腹腔内用强毒福氏 2a 志贺菌（YSH6000）攻击导致成年 B6 小鼠腹泻和严重体重减轻。值得注意的是，强毒福氏 2a 志贺菌不仅可以侵袭和定植全身组织，还可以侵袭和定植大肠的浆膜和固有层区域。此外，在腹腔内志贺氏菌感染后 24 小时，大肠中发现上皮脱落、屏障完整性和杯状细胞增生。值得注意的是，腹腔内攻击后大肠中主要表达促炎细胞因子和趋化因子。单核细胞在减轻腹泻和提供针对腹腔内志贺氏菌感染的保护作用方面发挥关键作用。最重要的是，用减毒福氏 2a 志贺菌（SC602）株预先接种的小鼠可免受 YSH6000 的腹腔内攻击。综上所述，这些发现表明，腹腔内用强毒福氏 2a 志贺菌攻击可引起成年小鼠细菌性痢疾和严重发病机制。该模型可能有助于理解细菌性痢疾的诱导机制，并评估志贺氏菌候选疫苗。
