title: Autophagy controls an intrinsic host defense to bacteria by promoting epithelial cell survival: a murine model.
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 death in the intestine. During this process, autophagy proceeded without any signs of inflammation. In contrast, blocking autophagy in epithelial cells enhanced host cell death, leading to tissue destruction and to inflammation, suggesting that autophagic flow relieves cellular stress associated with host cell death and inflammation. Herein we propose a new concept of "epithelial barrier turnover" as a general intrinsic host defense mechanism that increases survival of host cells and inhibits inflammation against enteric bacterial infections, which is regulated by autophagy.
authors.affiliation: Mucosal Immunology Section, Laboratory Science Division, International Vaccine Institute, Seoul, Korea ; Laboratory of Microbiology, College of Pharmacy, Ajou University, Suwon, Kyeonggi-do, Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Chang
authors.forename: Se-Na
authors.initials: SN
authors.lastname: Lee
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Yang
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hyun-Jeong
authors.initials: HJ
authors.lastname: Ko
authors.forename: Michinaga
authors.initials: M
authors.lastname: Ogawa
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sasakawa
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000235:genetics*; D058491:Bacterial Load; D002470:Cell Survival; D004405:Dysentery, Bacillary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D019879:Paneth Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D010581:Peyer's Patches / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D012763:Shigella flexneri / Q000276:immunology*