小柯机器人

FPR1是宿主免疫细胞上的鼠疫受体
2019-09-19 14:50

美国阿贡国家实验室Dominique Missiakas研究组发现N-甲酰基肽受体(FPR1)是宿主免疫细胞上的鼠疫受体。 2019年9月18日在线出版的《自然》发表了这项成果。

研究者发现在人体免疫细胞中鼠疫杆菌III型分泌系统的针帽状蛋白LcrV与N-甲酰基肽受体(FPR1)结合促进细菌效应物的转运。小鼠的瘟疫感染是特点是死亡率高,然而,Fpr1缺失小鼠的存活率升高并且增强了对抗鼠疫病毒的抗体反应。研究者鉴定了FPR1R190W是人体中保护中性粒细胞免受鼠疫杆菌III型分泌系统破坏的候选等位基因。因此,FPR1是人和小鼠体内保守的鼠疫受体,它的缺失或突变提高宿主对鼠疫杆菌的抵御。此外,鼠疫选择的FPR1等位基因似乎已形成对其他传染病和恶性肿瘤的免疫反应。

据介绍,鼠疫耶尔森氏菌利用III型分泌系统分泌的的致病因子选择性地破坏宿主免疫细胞,并且鼠疫耶尔森氏菌在血液中繁殖并通过跳蚤传播给新宿主。不过,导致鼠疫细菌选择性破坏免疫细胞的主要因子尚不清楚。

附:英文原文

Title: FPR1 is the plague receptor on host immune cells

Author: Patrick Osei-Owusu, Thomas M. Charlton, Hwan Keun Kim, Dominique Missiakas, Olaf Schneewind

Issue&Volume: 2019-09-18

Abstract: 

The causative agent of plague, Yersinia pestis, uses a type III secretion system to selectively destroy immune cells in humans, thus enabling Y. pestis to reproduce in the bloodstream and be transmitted to new hosts through fleabites. The host factors that are responsible for the selective destruction of immune cells by plague bacteria are unknown. Here we show that LcrV, the needle cap protein of the Y. pestis type III secretion system, binds to the N-formylpeptide receptor (FPR1) on human immune cells to promote the translocation of bacterial effectors. Plague infection in mice is characterized by high mortality; however, Fpr1-deficient mice have increased survival and antibody responses that are protective against plague. We identified FPR1R190W as a candidate resistance allele in humans that protects neutrophils from destruction by the Y. pestis type III secretion system. Thus, FPR1 is a plague receptor on immune cells in both humans and mice, and its absence or mutation provides protection against Y. pestis. Furthermore, plague selection of FPR1 alleles appears to have shaped human immune responses towards other infectious diseases and malignant neoplasms.

DOI: 10.1038/s41586-019-1570-z

Source:https://www.nature.com/articles/s41586-019-1570-z

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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