A Mouse Model of Shigellosis by Intraperitoneal Infection

다국어 초록 (Multilingual Abstract)

<P>In human and nonhuman primates, <I>Shigella spp.</I> cause bacillary dysentery by invading colon epithelium and promoting a strong inflammatory response; however, adult mice are resistant to oral <I>Shigella</I> infection. In this study, intraperitoneal challenge with virulent <I>S. flexneri</I> 2a (YSH6000) resulted in diarrhea and severe body weight loss in adult B6 mice. Of note, virulent <I>S. flexneri</I> 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 <I>Shigella</I> 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 <I>Shigella</I> infection. Most importantly, mice prevaccinated with attenuated <I>S. flexneri</I> 2a (SC602) strain were protected against intraperitoneal challenge with YSH6000. When taken together, these findings show that intraperitoneal challenge with virulent <I>S. flexneri</I> 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 <I>Shigella</I> vaccine candidates.</P>