Porphyromonas gingivalis Peptidoglycans Induce Excessive Activation of the Innate Immune System in Silkworm Larvae
Porphyromonas gingivalis Peptidoglycans Induce Excessive Activation of the Innate Immune System in Silkworm Larvae
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DOI：
10.1074/jbc.m110.112987
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发表时间：
2010-10-22
影响因子：
4.8
通讯作者：
Sekimizu, Kazuhisa
中科院分区：
文献类型：
--
作者：
Ishii, Kenichi;Hamamoto, Hiroshi;Sekimizu, Kazuhisa
牙龈卟啉单胞菌是一种引起人类牙周组织炎症的病原体，将家蚕（家蚕，鳞翅目）的幼虫注射到血液中（血淋巴）后会死亡。蚕的致死率并没有通过抗生素治疗而恢复，热杀细菌也是致命的。缺乏毒力因子的牙龈假单胞菌突变株热杀菌也能杀死家蚕。家蚕注射从牙龈假单胞菌（P. gingivalis, pPG）中纯化的肽聚糖（peptide - gly聚糖降解酶）后死亡。pPG诱导家蚕血淋巴黑化的剂量与杀死家蚕所需剂量相同。pPG注射液可提高家蚕组织中caspase的活性。通过注射黑化抑制试剂（丝氨酸蛋白酶抑制剂和1-苯基-2-硫脲）、抗氧化剂（n-乙酰- l-半胱氨酸、谷胱甘肽和过氧化氢酶）和半胱天冬酶抑制剂（Ac-DEVD-CHO）延缓ppg诱导的家蚕死亡。因此，pPG诱导先天免疫反应的过度激活，导致宿主组织中活性氧的产生和凋亡细胞的死亡。
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.