Borrelia species induce inflammasome activation and IL-17 production through a caspase-1-dependent mechanism
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Publication year
2011Source
European Journal of Immunology, 41, 1, (2011), pp. 172-81ISSN
Publication type
Article / Letter to editor
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Organization
Internal Medicine
Medical Microbiology
Journal title
European Journal of Immunology
Volume
vol. 41
Issue
iss. 1
Page start
p. 172
Page end
p. 81
Subject
N4i 1: Pathogenesis and modulation of inflammation NCMLS 1: Infection and autoimmunity; N4i 2: Invasive mycoses and compromised host NCMLS 1: Infection and autoimmunityAbstract
Borrelia burgdorferi spirochetes cause Lyme disease, which can result in severe clinical symptoms such as multiple joint inflammation and neurological disorders. IFN-gamma 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-1beta has been linked to the generation of IL-17-producing T cells, whereas caspase-1-mediated IL-18 is crucial for IFN-gamma 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-gamma and IL-17 production after Borrelia stimulation. A lack of IL-1beta was responsible for the defective IL-17 production, whereas IL-18 was crucial for the IFN-gamma production. Caspase-1-dependent IL-33 played no role in the Borrelia-induced production of IL-1beta, IFN-gamma 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.
This item appears in the following Collection(s)
- Academic publications [245263]
- Electronic publications [132514]
- Faculty of Medical Sciences [93208]
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