title: Role of proapoptotic BH3-only proteins in Listeria monocytogenes infection.
abstract: The ability of pathogens to influence host cell survival is a crucial virulence factor. Listeria monocytogenes (Lm) infection is known to be associated with severe apoptosis of hepatocytes and spleen cells. This impairs host defense mechanisms and thereby facilitates the spread of intracellular pathogens. The general mechanisms of apoptosis elicited by Lm infection are understood, however, the roles of BH3-only proteins during primary Lm infection have not been examined. To explore the roles of BH3-only proteins in Lm-induced apoptosis, we studied Listeria infections in mice deficient in Bim, Bid, Noxa or double deficient in BimBid or BimNoxa. We found that BimNoxa double knockout mice were highly resistant to high-dose challenge with Listeria. Decreased bacterial burden and decreased host cell apoptosis were found in the spleens of these mice. The ability of the BH3-deficient mice to clear bacterial infection more efficiently than WT was correlated with increased concentrations of ROS, neutrophil extracellular DNA trap release and downregulation of TNF-α. Our data show a novel pathway of infection-induced apoptosis that enhances our understanding of the mechanism by which BH3-only proteins control apoptotic host cell death during Listeria infection.
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Camilla
authors.initials: C
authors.lastname: Margaroli
authors.affiliation: Swiss Vaccine Research Institute, Centre des laboratoires d'Epalinges, Epalinges, Switzerland.|Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Oberle
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Christine
authors.initials: C
authors.lastname: Lavanchy
authors.affiliation: Swiss Vaccine Research Institute, Centre des laboratoires d'Epalinges, Epalinges, Switzerland.|Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Scherer
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Muriel
authors.initials: M
authors.lastname: Rosa
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|The Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.|The Department of Medical Biology, University of Melbourne, Melbourne, Australia.
authors.forename: Marc
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: Technische Universität München, Weihenstephaner Berg 3, 85354 Freising-Weihenstephan, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Zehn
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Hans
authors.initials: H
authors.lastname: Acha-Orbea
authors.affiliation: Department of Biochemistry CIIL, University of Lausanne, Epalinges, Switzerland.
authors.forename: Driss
authors.initials: D
authors.lastname: Ehirchiou
mesh_terms: D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000172:deficiency; D000072224:Bcl-2-Like Protein 11 / Q000172:deficiency; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D004198:Disease Susceptibility; D065206:Extracellular Traps / Q000276:immunology; D005260:Female; D015870:Gene Expression; D008089:Listeria monocytogenes; D008088:Listeriosis / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000378:metabolism*; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; D000072224:Bcl-2-Like Protein 11; D016207:Cytokines; D024101:Mitochondrial Proteins; C408009:Pmaip1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species
keywords: Apoptosis; Cytokines; Host-pathogens interactions; Immune evasion; TNF; Transgenic models