Deficiency of hasB accelerated the clearance of Streptococcus equi subsp. Zooepidemicus through gasdermin d-dependent neutrophil extracellular traps.
Int Immunopharmacol
; 140: 112829, 2024 Oct 25.
Article
em En
| MEDLINE
| ID: mdl-39083933
ABSTRACT
Streptococcus equi subsp. zooepidemicus (S. zooepidemicus, SEZ) is an essential zoonotic bacterial pathogen that can cause various inflammation, such as meningitis, endocarditis, and pneumonia. UDP-glucose dehydrogenase (hasB) is indispensable in synthesizing SEZ virulence factor hyaluronan capsules. Our study investigated the infection of hasB on mice response to SEZ by employing a constructed capsule-deficient mutant strain designated as the ΔhasB strain. This deficiency was associated with a reduced SEZ bacterial load in the mice's blood and peritoneal lavage fluid (PLF) post-infection. Besides, the ΔhasB SEZ strain exhibited a higher propensity for neutrophil infiltration and release of cell-free DNA (cfDNA) in vivo compared to the wild-type (WT) SEZ strain. In vitro experiments further revealed that ΔhasB SEZ more effectively induced the formation of neutrophil extracellular traps (NETs) containing histone 3 (H3), neutrophil elastase (NE), and DNA, than its WT counterpart. Moreover, the release of NETs was determined to be gasdermin D (GSDMD)-dependent during the infection process. Taken together, these findings underscore that the deficiency of the hasB gene in SEZ leads to enhanced GSDMD-dependent NET release from neutrophils, thereby reducing SEZ's capacity to resist NETs-mediated eradication during infection. Our finding paves the way for the development of innovative therapeutic strategies against SEZ.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Estreptocócicas
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Streptococcus equi
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Proteínas de Ligação a Fosfato
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Armadilhas Extracelulares
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Neutrófilos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Int Immunopharmacol
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Int. immunopharmacol
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International immunopharmacology
Ano de publicação:
2024
Tipo de documento:
Article