title: AIM2 contributes to the maintenance of intestinal integrity via Akt and protects against Salmonella mucosal infection.
abstract: The mechanism regulating the gastrointestinal epithelial barrier remains poorly understood. We herein demonstrate that Absent in melanoma-2 (AIM2) contributes to the maintenance of intestinal barrier integrity and defense against bacterial infection. AIM2-deficient mice displayed an increased susceptibility to mucosal but not systemic infection by Salmonella typhimurium, indicating a protective role for AIM2 in the gastrointestinal tract. In a Salmonella colitis model, compared with wild-type mice, AIM2(-/-) mice exhibited more severe body weight loss, intestinal damage, intestinal inflammation, and disruption of basal and activated epithelial cell turnover. In vivo and in vitro data showed that AIM2 restricted the early epithelial paracellular invasion of Salmonella and decreased epithelial permeability. The decreased epithelial barrier in AIM2(-/-) mice might be attributed to the altered expression of tight junction proteins that contribute to epithelial integrity. AIM2 promoted the expression of tight junction proteins through Akt activation. Together, these results suggest that AIM2 is required for maintaining the integrity of the epithelial barrier.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine & The First Hospital, Jilin University, Changchun, China.
authors.forename: G-Q
authors.initials: GQ
authors.lastname: Hu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine & The First Hospital, Jilin University, Changchun, China.
authors.forename: P-X
authors.initials: PX
authors.lastname: Song
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine & The First Hospital, Jilin University, Changchun, China.
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine & The First Hospital, Jilin University, Changchun, China.
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine & The First Hospital, Jilin University, Changchun, China.
authors.forename: Q-Q
authors.initials: QQ
authors.lastname: Lei
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine & The First Hospital, Jilin University, Changchun, China.
authors.forename: S-X
authors.initials: SX
authors.lastname: Yu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine & The First Hospital, Jilin University, Changchun, China.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine & The First Hospital, Jilin University, Changchun, China.
authors.forename: C-T
authors.initials: CT
authors.lastname: Du
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine & The First Hospital, Jilin University, Changchun, China.
authors.forename: X-M
authors.initials: XM
authors.lastname: Deng
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine & The First Hospital, Jilin University, Changchun, China.
authors.forename: W-Y
authors.initials: WY
authors.lastname: Han
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine & The First Hospital, Jilin University, Changchun, China.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D002432:Cecum / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D062465:Claudin-3 / Q000235:genetics / Q000276:immunology; D003092:Colitis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010539:Permeability; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology*; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012486:Salmonella typhimurium / Q000254:growth & development / Q000276:immunology; D012720:Severity of Illness Index; D015398:Signal Transduction; D016019:Survival Analysis; D019108:Tight Junctions / Q000276:immunology / Q000382:microbiology / Q000473:pathology
chemical_list: C540422:Aim2 protein, mouse; D062465:Claudin-3; C568123:Cldn3 protein, mouse; D016207:Cytokines; D004268:DNA-Binding Proteins; D051057:Proto-Oncogene Proteins c-akt
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