Septins restrict inflammation and protect zebrafish larvae from Shigella infection

PLoS Pathogens

Avinash R. Shenoy¹  Laurent Boucontet²  Serge Mostowy²  Alexandra R. Willis³  Emma Colucci-Guyon³  Maria J. Mazon-Moya³  Vincenzo Torraca³ 

[1] CNRS, UMR 3738, Paris, France;Institut Pasteur, Unité Macrophages et Développement de l'Immunité, Département de Biologie du Développement et des Cellules Souches, Paris, France;Section of Microbiology, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London, United Kingdom

关键词: Larvae;    Shigella flexneri;    Neutrophils;    Zebrafish;    Shigellosis;    Septins;    Inflammation;    Macrophages;   

DOI  :  10.1371/journal.ppat.1006467

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY