Distinct Functions of Bombyx mori Peptidoglycan Recognition Protein 2 in Immune Responses to Bacteria and Viruses

Distinct Functions of Bombyx mori Peptidoglycan Recognition Protein 2 in Immune Responses to Bacteria and Viruses
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家蚕肽聚糖识别蛋白 2 在细菌和病毒免疫反应中的独特功能

DOI:
10.3389/fimmu.2019.00776
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发表时间:
2019-04-12
影响因子:
7.3
通讯作者:
Xia, Qingyou
Xia, Qingyou
中科院分区:
医学2区
文献类型:
--
作者:
Jiang, Liang;Liu, Weiqiang;Xia, Qingyou

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肽聚糖识别蛋白(PGRP)是昆虫天然免疫中重要的模式识别受体,在昆虫识别细菌和防御细菌中起着重要作用。很少有研究报道PGRP在病毒感染中的作用。在这里,我们从模式鳞翅目家蚕中克隆了两种形式的PGRP:BmPGRP 2 -1是一种跨膜蛋白,而BmPGRP 2 -2是一种细胞内蛋白。BmPGRP 2 -1与二氨基庚二酸(DAP)型肽聚糖(PGN)结合以激活典型免疫缺陷(Imd)途径。BmPGRP 2 -2敲低减少了B。家蚕核型多角体病毒(BmNPV)的增殖和死亡率在细胞系和家蚕幼虫,而其过表达增加病毒复制。转录组和定量PCR(qPCR)结果证实BmPGRP 2负调节磷酸酶和张力蛋白同源物(PTEN)。BmNPV诱导BmPGRP 2 -2表达,并通过抑制PTEN-PI 3 K/Akt信号通路抑制细胞凋亡,提示BmNPV通过调节BmPGRP 2 -2-PTEN-PI 3 K/Akt信号通路逃避宿主的抗病毒防御。这些结果表明BmPGRP 2的两种形式在宿主对细菌和病毒的应答中具有不同的功能。
Peptidoglycan recognition protein (PGRP) is an important pattern recognition receptor in innate immunity that is vital for bacterial recognition and defense in insects. Few studies report the role of PGRP in viral infection. Here we cloned two forms of PGRP from the model lepidopteran Bombyx mori: BmPGRP2-1 is a transmembrane protein, whereas BmPGRP2-2 is an intracellular protein. BmPGRP2-1 bound to diaminopimelic acid (DAP)-type peptidoglycan (PGN) to activate the canonical immune deficiency (Imd) pathway. BmPGRP2-2 knockdown reduced B. mori nucleopolyhedrovirus (BmNPV) multiplication and mortality in cell lines and in silkworm larvae, while its overexpression increased viral replication. Transcriptome and quantitative PCR (qPCR) results confirmed that BmPGRP2 negatively regulated phosphatase and tensin homolog (PTEN). BmPGRP2-2 expression was induced by BmNPV, and the protein suppressed PTEN-phosphoinositide 3-kinase (PI3K)/Akt signaling to inhibit cell apoptosis, suggesting that BmNPV modulates BmPGRP2-2-PTEN-PI3K/Akt signaling to evade host antiviral defense. These results demonstrate that the two forms of BmPGRP2 have different functions in host responses to bacteria and viruses.