Borrelia species induce inflammasome activation and IL-17 production through a caspase-1-dependent mechanism.
Eur J Immunol
; 41(1): 172-81, 2011 Jan.
Article
em En
| MEDLINE
| ID: mdl-21182088
ABSTRACT
Borrelia burgdorferi spirochetes cause Lyme disease, which can result in severe clinical symptoms such as multiple joint inflammation and neurological disorders. IFN-γ and IL-17 have been suggested to play an important role in the host defense against Borrelia, and in the immunopathology of Lyme disease. The caspase-1-dependent cytokine IL-1ß has been linked to the generation of IL-17-producing T cells, whereas caspase-1-mediated IL-18 is crucial for IFN-γ production. In this study, we show by using knockout mice the role of inflammasome-activated caspase-1 in the regulation of cytokine responses by B. burgdorferi. Caspase-1-deficient cells showed significantly less IFN-γ and IL-17 production after Borrelia stimulation. A lack of IL-1ß was responsible for the defective IL-17 production, whereas IL-18 was crucial for the IFN-γ production. Caspase-1-dependent IL-33 played no role in the Borrelia-induced production of IL-1ß, IFN-γ or IL-17. In conclusion, we describe for the first time the role of the inflammasome-dependent caspase-1 activation of cytokines in the regulation of IL-17 production induced by Borrelia spp. As IL-17 has been implicated in the pathogenesis of chronic Lyme disease, these data suggest that caspase-1 targeting may represent a new immunomodulatory strategy for the treatment of complications of late stage Lyme disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Borrelia
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Doença de Lyme
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Caspase 1
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Interleucina-17
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Inflamassomos
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article