title: Porphyromonas gingivalis peptidoglycans induce excessive activation of the innate immune system in silkworm larvae.
abstract: Porphyromonas gingivalis, a pathogen that causes inflammation in human periodontal tissue, killed silkworm (Bombyx mori, Lepidoptera) larvae when injected into the blood (hemolymph). Silkworm lethality was not rescued by antibiotic treatment, and heat-killed bacteria were also lethal. Heat-killed bacteria of mutant P. gingivalis strains lacking virulence factors also killed silkworms. Silkworms died after injection of peptidoglycans purified from P. gingivalis (pPG), and pPG toxicity was blocked by treatment with mutanolysin, a peptidoglycan-degrading enzyme. pPG induced silkworm hemolymph melanization at the same dose as that required to kill the animal. pPG injection increased caspase activity in silkworm tissues. pPG-induced silkworm death was delayed by injecting melanization-inhibiting reagents (a serine protease inhibitor and 1-phenyl-2-thiourea), antioxidants (N-acetyl-l-cysteine, glutathione, and catalase), and a caspase inhibitor (Ac-DEVD-CHO). Thus, pPG induces excessive activation of the innate immune response, which leads to the generation of reactive oxygen species and apoptotic cell death in the host tissue.
authors: From the Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors: Kenichi
authors: K
authors: Ishii
authors: From the Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors: Hiroshi
authors: H
authors: Hamamoto
authors: From the Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors: Katsutoshi
authors: K
authors: Imamura
authors: From the Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors: Tatsuo
authors: T
authors: Adachi
authors: Division of Microbiology and Oral Infection, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors: Mikio
authors: M
authors: Shoji
authors: Division of Microbiology and Oral Infection, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
authors: Koji
authors: K
authors: Nakayama
authors: From the Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan. Electronic address: sekimizu@mol.f.u-tokyo.ac.jp.
authors: Kazuhisa
authors: K
authors: Sekimizu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D016866:Bacteroidaceae Infections / Q000276:immunology / Q000382:microbiology; D012831:Bombyx / Q000276:immunology* / Q000382:microbiology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006458:Hemolymph / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects* / Q000502:physiology; D007814:Larva / Q000276:immunology / Q000382:microbiology; D010457:Peptidoglycan / Q000276:immunology* / Q000494:pharmacology; D010518:Periodontitis / Q000276:immunology / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000276:immunology* / Q000472:pathogenicity; D017382:Reactive Oxygen Species / Q000276:immunology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D015853:Cysteine Proteinase Inhibitors; D010457:Peptidoglycan; D017382:Reactive Oxygen Species; D015842:Serine Proteinase Inhibitors