Septins restrict inflammation and protect zebrafish larvae from Shigella infection
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Shigella flexneri, a Gram-negative enteroinvasive pathogen, causes inflammatory destruction of the human intestinal epithelium. Infection by S. flexneri has been well-studied in vitro and is a paradigm for bacterial interactions with the host immune system. Recent work has revealed that components of the cytoskeleton have important functions in innate immunity and inflammation control. Septins, highly conserved cytoskeletal proteins, have emerged as key players in innate immunity to bacterial infection, yet septin function in vivo is poorly understood. Here, we use S. flexneri infection of zebrafish (Danio rerio) larvae to study in vivo the role of septins in inflammation and infection control. We found that depletion of Sept15 or Sept7b, zebrafish orthologs of human SEPT7, significantly increased host susceptibility to bacterial infection. Live-cell imaging of Sept15-depleted larvae revealed increasing bacterial burdens and a failure of neutrophils to control infection. Strikingly, Sept15-depleted larvae present significantly increased activity of Caspase-1 and more cell death upon S. flexneri infection. Dampening of the inflammatory response with anakinra, an antagonist of interleukin-1 receptor (IL-1R), counteracts Sept15 deficiency in vivo by protecting zebrafish from hyper-inflammation and S. flexneri infection. These findings highlight a new role for septins in host defence against bacterial infection, and suggest that septin dysfunction may be an underlying factor in cases of hyper-inflammation.
Date Issued
2017-06-26
Date Acceptance
2017-06-12
Citation
PLoS Pathogens, 2017, 13 (6), pp.1-23
ISSN
1553-7366
Publisher
Public Library of Science (PLoS)
Start Page
1
End Page
23
Journal / Book Title
PLoS Pathogens
Volume
13
Issue
6
Copyright Statement
© 2017 Mazon-Moya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000404511700050&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Microbiology
Parasitology
Virology
NLRP3 INFLAMMASOME
CELL-DEATH
INTERLEUKIN-1-RECEPTOR ANTAGONIST
AUTOINFLAMMATORY DISEASE
HOST-DEFENSE
ACTIVATION
MACROPHAGES
MITOCHONDRIA
INHIBITION
AUTOPHAGY
Publication Status
Published
Article Number
ARTN e1006467
Date Publish Online
2017-06-26