title: Serratia marcescens induces apoptotic cell death in host immune cells via a lipopolysaccharide- and flagella-dependent mechanism.
abstract: Injection of Serratia marcescens into the blood (hemolymph) of the silkworm, Bombyx mori, induced the activation of c-Jun NH(2)-terminal kinase (JNK), followed by caspase activation and apoptosis of blood cells (hemocytes). This process impaired the innate immune response in which pathogen cell wall components, such as glucan, stimulate hemocytes, leading to the activation of insect cytokine paralytic peptide. S. marcescens induced apoptotic cell death of silkworm hemocytes and mouse peritoneal macrophages in vitro. We searched for S. marcescens transposon mutants with attenuated ability to induce apoptosis of silkworm hemocytes. Among the genes identified, disruption mutants of wecA (a gene involved in lipopolysaccharide O-antigen synthesis), and flhD and fliR (essential genes in flagella synthesis) showed reduced motility and impaired induction of mouse macrophage cell death. These findings suggest that S. marcescens induces apoptosis of host immune cells via lipopolysaccharide- and flagella-dependent motility, leading to the suppression of host innate immunity.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ishii
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Adachi
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Imamura
authors.forename: Shinya
authors.initials: S
authors.lastname: Takano
authors.forename: Kimihito
authors.initials: K
authors.lastname: Usui
authors.forename: Kazushi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sekimizu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D012831:Bombyx / Q000276:immunology* / Q000382:microbiology; D005407:Flagella / Q000276:immunology*; D006434:Hemocytes / Q000276:immunology* / Q000382:microbiology; D007113:Immunity, Innate; D008070:Lipopolysaccharides / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000382:microbiology; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D016868:Serratia Infections / Q000276:immunology* / Q000382:microbiology; D012706:Serratia marcescens / Q000276:immunology* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C085248:FliR protein, Bacteria; D008070:Lipopolysaccharides; D008565:Membrane Proteins