Monomeric and polymeric gram-negative peptidoglycan but not purified LPS stimulate the Drosophila IMD pathway
Monomeric and polymeric gram-negative peptidoglycan but not purified LPS stimulate the Drosophila IMD pathway
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DOI：
10.1016/s1074-7613(04)00104-9
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发表时间：
2004-05-01
期刊：
影响因子：
32.4
通讯作者：
Silverman, N
中科院分区：
文献类型：
--
作者：
Kaneko, T;Goldman, WE;Silverman, N
昆虫完全依靠先天免疫反应在感染后存活。这些反应包括激活细胞外的蛋白酶级联，导致黑化和凝血，以及细胞内诱导抗菌肽基因表达的信号转导途径。在果蝇中，IMD途径是抗菌素基因表达所必需的，以响应革兰氏阴性细菌。这些细菌中激活IMD途径的确切分子成分(S)仍然存在争议。我们发现，高纯度的内毒素不能刺激IMD途径。然而，哺乳动物中脂多糖的活性部分类脂A激活了家蚕的黑化。另一方面，IMD途径对聚合物和单体革兰氏阴性肽聚糖非常敏感。识别肽聚糖需要革兰氏阴性肽聚糖和受体PGRP-LC所特有的茎-肽序列。识别单体和多聚肽聚糖需要不同的PGRP-LC剪接异构体，而识别类脂A需要家蚕血淋巴中一种未知的可溶性因子。
Insects depend solely upon innate immune responses to survive infection. These responses include the activation of extracellular protease cascades, leading to melanization and clotting, and intracellular signal transduction pathways inducing antimicrobial peptide gene expression. In Drosophila, the IMD pathway is required for antimicrobial gene expression in response to gram-negative bacteria. The exact molecular component(s) from these bacteria that activate the IMD pathway remain controversial. We found that highly purified LPS did not stimulate the IMD pathway. However, lipid A, the active portion of LPS in mammals, activated melanization in the silkworm Bombyx morii. On the other hand, the IMD pathway was remarkably sensitive to polymeric and monomeric gram-negative peptidoglycan. Recognition of peptidoglycan required the stem-peptide sequence specific to gram-negative peptidoglycan and the receptor PGRP-LC. Recognition of monomeric and polymeric peptidoglycan required different PGRP-LC splice isoforms, while lipid A recognition required an unidentified soluble factor in the hemolymph of Bombyx morii.