Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence.
Shigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the closely-related Shigella sonnei is replacing S. flexneri, especially in developing countries. The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) model of Sh...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1008006 |
| _version_ | 1818465769205268480 |
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| author | Vincenzo Torraca Myrsini Kaforou Jayne Watson Gina M Duggan Hazel Guerrero-Gutierrez Sina Krokowski Michael Hollinshead Thomas B Clarke Rafal J Mostowy Gillian S Tomlinson Vanessa Sancho-Shimizu Abigail Clements Serge Mostowy |
| author_facet | Vincenzo Torraca Myrsini Kaforou Jayne Watson Gina M Duggan Hazel Guerrero-Gutierrez Sina Krokowski Michael Hollinshead Thomas B Clarke Rafal J Mostowy Gillian S Tomlinson Vanessa Sancho-Shimizu Abigail Clements Serge Mostowy |
| author_sort | Vincenzo Torraca |
| collection | DOAJ |
| description | Shigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the closely-related Shigella sonnei is replacing S. flexneri, especially in developing countries. The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) model of Shigella infection, we discover that S. sonnei is more virulent than S. flexneri in vivo. Whole animal dual-RNAseq and testing of bacterial mutants suggest that S. sonnei virulence depends on its O-antigen oligosaccharide (which is unique among Shigella species). We show in vivo using zebrafish and ex vivo using human neutrophils that S. sonnei O-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enables S. sonnei to resist phagolysosome acidification and promotes neutrophil cell death. Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control of S. sonnei and zebrafish survival. Strikingly, larvae primed with a sublethal dose of S. sonnei are protected against a secondary lethal dose of S. sonnei in an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system against S. sonnei. Collectively, these findings reveal O-antigen as an important therapeutic target against bacillary dysentery, and may explain the rapidly increasing S. sonnei burden in developing countries. |
| first_indexed | 2024-04-13T20:50:01Z |
| format | Article |
| id | doaj.art-b235bb518caf42c7937d8bc6b7d9d890 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-04-13T20:50:01Z |
| publishDate | 2019-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-b235bb518caf42c7937d8bc6b7d9d8902022-12-22T02:30:34ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742019-12-011512e100800610.1371/journal.ppat.1008006Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence.Vincenzo TorracaMyrsini KaforouJayne WatsonGina M DugganHazel Guerrero-GutierrezSina KrokowskiMichael HollinsheadThomas B ClarkeRafal J MostowyGillian S TomlinsonVanessa Sancho-ShimizuAbigail ClementsSerge MostowyShigella flexneri is historically regarded as the primary agent of bacillary dysentery, yet the closely-related Shigella sonnei is replacing S. flexneri, especially in developing countries. The underlying reasons for this dramatic shift are mostly unknown. Using a zebrafish (Danio rerio) model of Shigella infection, we discover that S. sonnei is more virulent than S. flexneri in vivo. Whole animal dual-RNAseq and testing of bacterial mutants suggest that S. sonnei virulence depends on its O-antigen oligosaccharide (which is unique among Shigella species). We show in vivo using zebrafish and ex vivo using human neutrophils that S. sonnei O-antigen can mediate neutrophil tolerance. Consistent with this, we demonstrate that O-antigen enables S. sonnei to resist phagolysosome acidification and promotes neutrophil cell death. Chemical inhibition or promotion of phagolysosome maturation respectively decreases and increases neutrophil control of S. sonnei and zebrafish survival. Strikingly, larvae primed with a sublethal dose of S. sonnei are protected against a secondary lethal dose of S. sonnei in an O-antigen-dependent manner, indicating that exposure to O-antigen can train the innate immune system against S. sonnei. Collectively, these findings reveal O-antigen as an important therapeutic target against bacillary dysentery, and may explain the rapidly increasing S. sonnei burden in developing countries.https://doi.org/10.1371/journal.ppat.1008006 |
| spellingShingle | Vincenzo Torraca Myrsini Kaforou Jayne Watson Gina M Duggan Hazel Guerrero-Gutierrez Sina Krokowski Michael Hollinshead Thomas B Clarke Rafal J Mostowy Gillian S Tomlinson Vanessa Sancho-Shimizu Abigail Clements Serge Mostowy Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence. PLoS Pathogens |
| title | Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence. |
| title_full | Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence. |
| title_fullStr | Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence. |
| title_full_unstemmed | Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence. |
| title_short | Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence. |
| title_sort | shigella sonnei infection of zebrafish reveals that o antigen mediates neutrophil tolerance and dysentery incidence |
| url | https://doi.org/10.1371/journal.ppat.1008006 |
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