Autophagy Controls an Intrinsic Host Defense to Bacteria by Promoting Epithelial Cell Survival A Murine Model.docVIP

Autophagy Controls an Intrinsic Host Defense to Bacteria by Promoting Epithelial Cell Survival: A Murine Model Sun-Young Chang , Se-Na Lee , Jin-Young Yang , Dong Wook Kim , Joo-Heon Yoon , Hyun-Jeong 1,2 1 1 3 4 Ko , Michinaga Ogawa , Chihiro Sasakawa , Mi-Na Kweon 1,5 6 7,8 1* 1 Mucosal Immunology Section, Laboratory Science Division, International Vaccine Institute, Seoul, Korea, 2 Laboratory of Microbiology, College of Pharmacy, Ajou University, Suwon, Kyeonggi-do, Korea, 3 College of Pharmacy, Hanyang University, Ansan, Kyeonggi-do, Korea, 4 Department of Otorhinolaryngology, Yonsei University College of Medicine, Seodaemun-Gu, Seoul, Korea, 5 Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, Kangwon-do, Korea, 6 Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan, 7 Nippon Institute for Biological Science, Tokyo, Japan, 8 Medical Mycology Research Center, Chiba University, Chiba, Japan Abstract Cell death is a critical host response to regulate the fate of bacterial infections, innate immune responses, and ultimately, disease outcome. Shigella spp. invade and colonize gut epithelium in human and nonhuman primates but adult mice are naturally resistant to intra-gastric Shigella infection. In this study, however, we found Shigella could invade the terminal ileum of the mouse small intestine by 1 hour after infection and be rapidly cleared within 24 h. These early phase events occurred shortly after oral infection resulting in epithelial shedding, degranulation of Paneth cells, and cell de