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家蝇肽聚糖识别蛋白SC(PGRP-SC)的下调会导致抗菌肽的过度表达和化蛹延迟。

Downregulation of the Musca domestica peptidoglycan recognition protein SC (PGRP-SC) leads to overexpression of antimicrobial peptides and tardy pupation.

作者信息

Gao Yifu, Tang Ting, Gu Jihai, Sun Lingling, Gao Xiaobin, Ma Xianyong, Wang Xiaochun, Liu Fengsong, Wang Jianhui

机构信息

College of Life Sciences, Hebei University, Baoding, Hebei, China.

Department of Pathology, Yale University, New Haven, CT, USA.

出版信息

Mol Immunol. 2015 Oct;67(2 Pt B):465-74. doi: 10.1016/j.molimm.2015.08.007. Epub 2015 Aug 18.

DOI:10.1016/j.molimm.2015.08.007
PMID:26296288
Abstract

PGRP (peptidoglycan recognition protein) is a conserved protein family that recognizes the peptidoglycan in bacterial cell wall and causes the activation of various innate immune responses. Previous studies have reported that PGRP-SCs in Drosophila dampen the activation of Immune Deficiency (Imd) pathway to microbial infection, and participate in the lifespan extension of the insects. To facilitate understanding the function of PGRP-SCs from an evolutionary angle, we identified and functionally characterized the PGRP-SC gene in the housefly Musca domestica, a species that has adapted to a septic environment much harsher than the natural habitat of Drosophila. The gene designated as MdPGRP-SC was found most abundantly expressed in the 3rd instar larvae, and is expressed at this developmental stage predominantly in the gut. MdPGRP-SC was virtually unchanged in whole larvae after a septic injury at the second larval instar, while two antimicrobial peptides (AMPs), diptericin and attacin, were upregulated in the first 24h but not later. Through dsRNA microinjection, MdPGRP-SC was knocked down by RNA interference (RNAi), and caused the significant increased expression of diptericin and attacin. The pupation of MdPGRP-SC-depleted larvae was severely suppressed compared to controls. Opposite to the expression trend of MdPGRP-SC, a spontaneous active expression of diptericin and attacin was found in pre-pupae but not in third instar larvae. Taken together, our study reveals that downregulation of MdPGRP-SC leads to the overexpression of the AMPs, and is involved in the larvae-to-pupa transition of housefly.

摘要

肽聚糖识别蛋白(PGRP)是一个保守的蛋白家族,可识别细菌细胞壁中的肽聚糖并引发各种先天免疫反应的激活。先前的研究报道,果蝇中的PGRP-SC可抑制免疫缺陷(Imd)途径对微生物感染的激活,并参与昆虫寿命的延长。为了从进化角度便于理解PGRP-SC的功能,我们鉴定了家蝇(Musca domestica)中的PGRP-SC基因并对其进行了功能表征,家蝇是一种已适应比果蝇自然栖息地恶劣得多的腐败环境的物种。被命名为MdPGRP-SC的基因在三龄幼虫中表达最为丰富,并且在这个发育阶段主要在肠道中表达。在二龄幼虫期进行败血症损伤后,整个幼虫中的MdPGRP-SC几乎没有变化,而两种抗菌肽(AMPs),即双翅菌素和攻击素,在最初24小时内上调,但之后没有。通过双链RNA显微注射,MdPGRP-SC被RNA干扰(RNAi)敲低,并导致双翅菌素和攻击素的表达显著增加。与对照相比,MdPGRP-SC缺失的幼虫化蛹受到严重抑制。与MdPGRP-SC的表达趋势相反,在预蛹中发现双翅菌素和攻击素自发活跃表达,而在三龄幼虫中未发现。综上所述,我们的研究表明MdPGRP-SC的下调导致抗菌肽的过表达,并参与家蝇从幼虫到蛹的转变。

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