Shigella sonnei infection of zebrafish reveals that O-antigen mediates neutrophil tolerance and dysentery incidence.
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
24
07
2019
accepted:
01
11
2019
revised:
24
01
2020
pubmed:
13
12
2019
medline:
29
2
2020
entrez:
13
12
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31830135
doi: 10.1371/journal.ppat.1008006
pii: PPATHOGENS-D-19-01349
pmc: PMC6980646
doi:
Substances chimiques
O Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1008006Subventions
Organisme : MRF
ID : MRF_C0483
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N007727/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT097411MA
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206444/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P028225/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206508/Z/17/Z
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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