Borrelia species induce inflammasome activation and IL-17 production through a caspase-1-dependent mechanism.

Eur J Immunol 2011 Jan 9;41(1):172-81. Epub 2010 Dec 9.

Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

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-1β 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-1β 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-1β, 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.

Download full-text PDF

Source
http://dx.doi.org/10.1002/eji.201040385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3939779PMC
January 2011
27 Reads

Publication Analysis

Top Keywords

lyme disease
16
il-17 production
16
ifn-γ il-17
12
production caspase-1-dependent
8
il-18 crucial
8
crucial ifn-γ
8
ifn-γ production
8
production
7
il-17
7
ifn-γ
5
borrelia
5
inflammasome-activated caspase-1
4
cells caspase-1-mediated
4
role inflammasome-activated
4
disease data
4
caspase-1 regulation
4
regulation cytokine
4
burgdorferi caspase-1-deficient
4
responses burgdorferi
4
cytokine responses
4

Similar Publications