Septins restrict inflammation and protect zebrafish larvae from Shigella infection.
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 o...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-06-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006467&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849695152649535488 |
|---|---|
| author | Maria J Mazon-Moya Alexandra R Willis Vincenzo Torraca Laurent Boucontet Avinash R Shenoy Emma Colucci-Guyon Serge Mostowy |
| author_facet | Maria J Mazon-Moya Alexandra R Willis Vincenzo Torraca Laurent Boucontet Avinash R Shenoy Emma Colucci-Guyon Serge Mostowy |
| author_sort | Maria J Mazon-Moya |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-cbc5f72660c24379a1acddcf231f36fa |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2017-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-cbc5f72660c24379a1acddcf231f36fa2025-08-20T03:19:52ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-06-01136e100646710.1371/journal.ppat.1006467Septins restrict inflammation and protect zebrafish larvae from Shigella infection.Maria J Mazon-MoyaAlexandra R WillisVincenzo TorracaLaurent BoucontetAvinash R ShenoyEmma Colucci-GuyonSerge MostowyShigella 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006467&type=printable |
| spellingShingle | Maria J Mazon-Moya Alexandra R Willis Vincenzo Torraca Laurent Boucontet Avinash R Shenoy Emma Colucci-Guyon Serge Mostowy Septins restrict inflammation and protect zebrafish larvae from Shigella infection. PLoS Pathogens |
| title | Septins restrict inflammation and protect zebrafish larvae from Shigella infection. |
| title_full | Septins restrict inflammation and protect zebrafish larvae from Shigella infection. |
| title_fullStr | Septins restrict inflammation and protect zebrafish larvae from Shigella infection. |
| title_full_unstemmed | Septins restrict inflammation and protect zebrafish larvae from Shigella infection. |
| title_short | Septins restrict inflammation and protect zebrafish larvae from Shigella infection. |
| title_sort | septins restrict inflammation and protect zebrafish larvae from shigella infection |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1006467&type=printable |
| work_keys_str_mv | AT mariajmazonmoya septinsrestrictinflammationandprotectzebrafishlarvaefromshigellainfection AT alexandrarwillis septinsrestrictinflammationandprotectzebrafishlarvaefromshigellainfection AT vincenzotorraca septinsrestrictinflammationandprotectzebrafishlarvaefromshigellainfection AT laurentboucontet septinsrestrictinflammationandprotectzebrafishlarvaefromshigellainfection AT avinashrshenoy septinsrestrictinflammationandprotectzebrafishlarvaefromshigellainfection AT emmacolucciguyon septinsrestrictinflammationandprotectzebrafishlarvaefromshigellainfection AT sergemostowy septinsrestrictinflammationandprotectzebrafishlarvaefromshigellainfection |