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Journal Article
Decoy exosomes provide protection against bacterial toxins
2020
Overview
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
–
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-toxin
4
—a pore-forming toxin that binds the metalloprotease ADAM10 on the surface of a broad range of target cells and tissues
2
,
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.
In response to infection with
Staphylococcus aureus
in vitro and in vivo, host cells increase their secretion of exosomes containing ADAM10—vesicular structures that can provide protection by sequestering bacterial toxins.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/106
/ 13/109
/ 13/31
/ 42/41
/ 64/60
/ 82/1
/ 82/29
/ 82/81
/ Analysis
/ Animals
/ Autophagy-Related Proteins - metabolism
/ Bacteria
/ Bacterial Toxins - metabolism
/ Bacterial Toxins - pharmacology
/ Cell Survival - drug effects
/ Control
/ Decoys
/ DNA
/ DNA, Bacterial - pharmacology
/ Exosomes
/ Female
/ Humanities and Social Sciences
/ Humans
/ Male
/ Methicillin-Resistant Staphylococcus aureus - pathogenicity
/ Methicillin-Resistant Staphylococcus aureus - physiology
/ Mice
/ Proteins
/ Science
/ Staphylococcal Infections - mortality
/ Toxins
/ α-Toxin
