小柯机器人

宿主利用外泌体抵抗细菌毒素
2020-03-05 13:07

美国纽约大学医学院Ken Cadwell和Victor J. Torres团队合作的最新研究,揭示外泌体可作为诱饵来提供针对细菌毒素的保护作用。3月4日,《自然》在线发表了这一成果。

先前表明,自噬蛋白ATG16L1对于宿主抵抗编码α-毒素的耐甲氧西林的金黄色葡萄球菌(MRSA)菌株是必需的,α-毒素是一种成孔毒素,其与多种靶细胞和组织表面上的金属蛋白酶ADAM10结合。自噬通常涉及将胞质物靶向溶酶体进行降解。

研究人员发现ATG16L1和其他ATG蛋白通过在外泌体(内体来源的细胞外囊泡)上释放ADAM10介导了宿主针对α毒素的保护作用。细菌DNA和CpG DNA诱导人细胞以及小鼠分泌带有ADAM10的外泌体。体外实验表明转移的外泌体通过作为结合多种毒素的清除剂来保护宿主细胞,并且体内实验也证明其提高了感染MRSA小鼠的存活率。

这些发现表明,ATG蛋白在感染后介导了以前未知的防御形式,即促进了外泌体的释放作为细菌产生毒素的诱饵。

据悉,产生破坏宿主细胞质膜的成孔毒素是细菌病原体(如MRSA)的常见毒力来源。但是,尚不清楚宿主是否具有能够在感染过程中中和成孔毒素的先天免疫机制。

附:英文原文

Title: Decoy exosomes provide protection against bacterial toxins

Author: Matthew D. Keller, Krystal L. Ching, Feng-Xia Liang, Avantika Dhabaria, Kayan Tam, Beatrix M. Ueberheide, Derya Unutmaz, Victor J. Torres, Ken Cadwell

Issue&Volume: 2020-03-04

Abstract: The production of pore-forming toxins that disrupt the plasma membrane of host cells is a common virulence strategy for bacterial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA)1,2,3. It is unclear, however, whether host species possess innate immune mechanisms that can neutralize pore-forming toxins during infection. We previously showed that the autophagy protein ATG16L1 is necessary for protection against MRSA strains encoding α-toxin4—a pore-forming toxin that binds the metalloprotease ADAM10 on the surface of a broad range of target cells and tissues2,5,6. Autophagy typically involves the targeting of cytosolic material to the lysosome for degradation. Here we demonstrate that ATG16L1 and other ATG proteins mediate protection against α-toxin through the release of ADAM10 on exosomes—extracellular vesicles of endosomal origin. Bacterial DNA and CpG DNA induce the secretion of ADAM10-bearing exosomes from human cells as well as in mice. Transferred exosomes protect host cells in vitro by serving as scavengers that can bind multiple toxins, and improve the survival of mice infected with MRSA in vivo. These findings indicate that ATG proteins mediate a previously unknown form of defence in response to infection, facilitating the release of exosomes that serve as decoys for bacterially produced toxins.

DOI: 10.1038/s41586-020-2066-6

Source: https://www.nature.com/articles/s41586-020-2066-6

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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