GSDMD contributes to host defence against Staphylococcus aureus skin infection by suppressing the Cxcl1-Cxcr2 axis.
Vet Res
; 52(1): 71, 2021 May 19.
Article
em En
| MEDLINE
| ID: mdl-34011393
ABSTRACT
Gasdermin D (GSDMD), a member of the gasdermin protein family, is a caspase substrate, and its cleavage is required for pyroptosis and IL-1ß secretion. To date, the role and regulatory mechanism of GSDMD during cutaneous microbial infection remain unclear. Here, we showed that GSDMD protected against Staphylococcus aureus skin infection by suppressing Cxcl1-Cxcr2 signalling. GSDMD deficiency resulted in larger abscesses, more bacterial colonization, exacerbated skin damage, and increased inflammatory cell infiltration. Although GSDMD deficiency resulted in defective IL-1ß production, the critical role of IL-1ß was counteracted by the fact that Caspase-1/11 deficiency also resulted in less IL-1ß production but did not aggravate disease severity during S. aureus skin infection. Interestingly, GSDMD-deficient mice had increased Cxcl1 secretion accompanied by increased recruitment of neutrophils, whereas Caspase-1/11-deficient mice presented similar levels of Cxcl1 and neutrophils as wild-type mice. Moreover, the absence of GSDMD promoted Cxcl1 secretion in bone marrow-derived macrophages induced by live, dead, or different strains of S. aureus. Corresponding to higher transcription and secretion of Cxcl1, enhanced NF-κB activation was shown in vitro and in vivo in the absence of GSDMD. Importantly, inhibiting the Cxcl1-Cxcr2 axis with a Cxcr2 inhibitor or anti-Cxcl1 blocking antibody rescued host defence defects in the GSDMD-deficient mice. Hence, these results revealed an important role of GSDMD in suppressing the Cxcl1-Cxcr2 axis to facilitate pathogen control and prevent tissue damage during cutaneous S. aureus infection.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dermatopatias
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Infecções Estafilocócicas
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Staphylococcus aureus
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Receptores de Interleucina-8B
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Proteínas de Ligação a Fosfato
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Peptídeos e Proteínas de Sinalização Intracelular
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Quimiocina CXCL1
Limite:
Animals
Idioma:
En
Revista:
Vet Res
Assunto da revista:
MEDICINA VETERINARIA
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China