Specific pathways mediating inflammasome activation by Candida parapsilosis.

ABSTRACT: 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.

SUBMITTER: Toth A 

PROVIDER: S-EPMC5320503 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature