title: Crucial roles of TNFAIP8 protein in regulating apoptosis and Listeria infection.
abstract: TNF-α-induced protein 8 (TNFAIP8 or TIPE) is a newly described regulator of cancer and infection. However, its precise roles and mechanisms of actions are not well understood. We report in this article that TNFAIP8 regulates Listeria monocytogenes infection by controlling pathogen invasion and host cell apoptosis in a RAC1 GTPase-dependent manner. TNFAIP8-knockout mice were resistant to lethal L. monocytogenes infection and had reduced bacterial load in the liver and spleen. TNFAIP8 knockdown in murine liver HEPA1-6 cells increased apoptosis, reduced bacterial invasion into cells, and resulted in dysregulated RAC1 activation. TNFAIP8 could translocate to plasma membrane and preferentially associate with activated RAC1-GTP. The combined effect of reduced bacterial invasion and increased sensitivity to TNF-α-induced clearance likely protected the TNFAIP8-knockout mice from lethal listeriosis. Thus, by controlling bacterial invasion and the death of infected cells through RAC1, TNFAIP8 regulates the pathogenesis of L. monocytogenes infection.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; and.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Porturas
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; and.
authors.forename: Honghong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; and.
authors.forename: George
authors.initials: G
authors.lastname: Buchlis
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; and Department of Immunology, Shandong University School of Medicine, Ji'nan 250012, People's Republic of China.
authors.forename: Yunwei
authors.initials: Y
authors.lastname: Lou
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; and Department of Immunology, Shandong University School of Medicine, Ji'nan 250012, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; and.
authors.forename: Terry
authors.initials: T
authors.lastname: Cathopoulis
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; and.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Fayngerts
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; and.
authors.forename: Derek S
authors.initials: DS
authors.lastname: Johnson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; and.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104; and yhc@mail.med.upenn.edu.
authors.forename: Youhai H
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D006160:Guanosine Triphosphate / Q000378:metabolism; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011485:Protein Binding; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C550729:TNFAIP8 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D006160:Guanosine Triphosphate; D020830:rac1 GTP-Binding Protein