On the other hand, when IL-1β is highly produced by host cells af

On the other hand, when IL-1β is highly produced by host cells after Borrelia recognition, high levels of Th17 cells may be produced. Borrelia-primed Th17 cells might facilitate development of a chronic stage of Lyme disease, as already described in other diseases,

such as RA 41. At this moment, it is still unknown which specific T-cell population is responsible for the induction of IL-17 (CD4+,γδT cells, NK T cells, CD4−/CD8). One of our future plans is to detect which specific T-cell population is responsible for the induction of selleck chemicals IL-17 by Borrelia spp. In summary, Borrelia is a strong inducer of inflammasome activation and caspase-1-mediated IL-1β induction amplifies the production of IL-17 after Borrelia exposure. The Borrelia-induced IL-17 production is modulated by the IL-18-driven IFN-γ. These data indicate that caspase-1-dependent cytokines IL-1β AZD6244 cost and IL-18 determine the development and clinical outcome of Lyme disease, which was also demonstrated by our in vivo data. These findings give more insight into the pathogenesis of Lyme disease

and may provide useful information for the development of new therapeutic strategies targeting the inflammasome. B. burgdorferi pKo strain and B. afzelii, patient isolate were cultured at 33°C in Barbour-Stoenner-Kelley -H medium (Sigma-Aldrich) supplemented with 6% rabbit serum. Spirochetes were grown to late-logarithmic phase and examined for motility by dark-field microscopy. Organisms were quantitated by fluorescence microscopy after mixing 10 μL aliquots of the culture material with 10 μL of an acridine orange solution to concentrations. Bacteria were harvested by centrifugation of the culture at 7000×g for 15 min, washed twice with sterile PBS (pH 7.4), and diluted in the specified medium to required concentrations of 1–3×106 spirochetes per mL. Heat-killed B. burgdorferi and B. afzelii were prepared by heating at 52°C for 30 min before dilution. Heat-inactivated bacteria

were used according to Wang et al. 6. C57BL/6 and Balb/c mice were obtained from Charles River Wiga (Sulzfeld, Germany). IL-1β gene-deficient mice were kindly Thiamet G provided by J. Mudgett, Merck (Rahway, NJ, USA). Caspase-1-deficient mice were originally obtained from R. A. Flavell, New Haven, CT, USA and generation of these mice was previously described 49, 50. The generation of IL-18 knockout mice was previously described 51. Male WT and knockout mice between 6 and 8 wk of age were used. The mice were fed with sterilized laboratory chow (Hope Farms, Woerden, The Netherlands) and water ad libitum. The experiments were approved by the Ethics Committee on Animal Experiments of the Radboud University, Nijmegen. Bone marrow from mice (age between 8 and 20 wks) was flushed out after dissecting mouse legs.

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