| First Author | Oosting M | Year | 2011 |
| Journal | Eur J Immunol | Volume | 41 |
| Issue | 1 | Pages | 172-81 |
| PubMed ID | 21182088 | Mgi Jnum | J:174656 |
| Mgi Id | MGI:5140287 | Doi | 10.1002/eji.201040385 |
| Citation | Oosting M, et al. (2011) Borrelia species induce inflammasome activation and IL-17 production through a caspase-1-dependent mechanism. Eur J Immunol 41(1):172-81 |
| abstractText | 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. |
