Serratia marcescens Induces Apoptotic Cell Death in Host Immune Cells via a Lipopolysaccharide- and Flagella-dependent Mechanism

• Published in: The Journal of biological chemistry 2012-10, Vol.287 (43), p.36582-36592
• Main Authors: Ishii, Kenichi, Adachi, Tatsuo, Imamura, Katsutoshi, Takano, Shinya, Usui, Kimihito, Suzuki, Kazushi, Hamamoto, Hiroshi, Watanabe, Takeshi, Sekimizu, Kazuhisa
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Apoptosis - immunology; Bacterial Proteins - immunology; Bombyx - immunology; Bombyx - microbiology; Flagella - immunology; Hemocytes - immunology; Hemocytes - microbiology; Immunity, Innate; Innate Immunity; Insect Immunity; Lipopolysaccharide (LPS); Lipopolysaccharides - immunology; Macrophages; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - microbiology; Membrane Proteins - immunology; Mice; Microbiology; Serratia Infections - immunology; Serratia Infections - microbiology; Serratia marcescens - immunology; Serratia marcescens - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M112.399667

Injection of Serratia marcescens into the blood (hemolymph) of the silkworm, Bombyx mori, induced the activation of c-Jun NH2-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. Background: The pathogenic mechanism of Serratia marcescens is poorly understood. Results:S. marcescens kills immune cells via an lipopolysaccharide- and flagella-dependent mechanism. Conclusion:S. marcescens suppresses innate immunity by killing immune cells. Significance: This is the first evidence to suggest that S. marcescens evades the immune system.