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Specific pathways mediating inflammasome activation by Candida parapsilosis #MMPMID28225025
Tóth A; Zajta E; Csonka K; Vágvölgyi C; Netea MG; Gácser A
Sci Rep 2017[]; 7 (ä): ä PMID28225025show ga
Candida albicans and C. parapsilosis are human pathogens causing severe infections. The NLRP3 inflammasome plays a crucial role in host defence against C. albicans, but it has been previously unknown whether C. parapsilosis activates this complex. Here we show that C. parapsilosis induces caspase-1 activation and interleukin-1? (IL-1?) secretion in THP-1, as well as primary, human macrophages. IL-1? secretion was dependent on NLRP3, K+-efflux, TLR4, IRAK, Syk, caspase-1, caspase-8 and NADPH-oxidase. Importantly, while C. albicans induced robust IL-1? release after 4?h, C. parapsilosis was not able to stimulate the production of IL-1? after this short incubation period. We also found that C. parapsilosis was phagocytosed to a lesser extent, and induced significantly lower ROS production and lysosomal cathepsin B release compared to C. albicans, suggesting that the low extent of inflammasome activation by C. parapsilosis may result from a delay in the so-called ?signal 2?. In conclusion, this is the first study to examine the molecular pathways responsible for the IL-1? production in response to a non-albicans Candida species, and these results enhance our understanding about the immune response against C. parapsilosis.