Porphyromonas gingivalis peptidoglycans induce excessive activation of the innate immune system in silkworm larvae.
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.
Ishii
Kenichi
K
From the Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Hamamoto
Hiroshi
H
From the Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Imamura
Katsutoshi
K
From the Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Adachi
Tatsuo
T
From the Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
Shoji
Mikio
M
Division of Microbiology and Oral Infection, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
Nakayama
Koji
K
Division of Microbiology and Oral Infection, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan.
Sekimizu
Kazuhisa
K
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.
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
D000975:Antioxidants; D015853:Cysteine Proteinase Inhibitors; D010457:Peptidoglycan; D017382:Reactive Oxygen Species; D015842:Serine Proteinase Inhibitors