Specific pathways mediating inflammasome activation by Candida parapsilosis

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Tóth Adél
Zajta Erik
Csonka Katalin
Vágvölgyi Csaba
Netea Mihai G.
Gácser Attila
Format: Article
Published: Nature Publishing Group 2017
Series:SCIENTIFIC REPORTS 7
doi:10.1038/srep43129

mtmt:3194164
Online Access:http://publicatio.bibl.u-szeged.hu/11086
Description
Summary: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-1beta (IL-1beta) secretion in THP-1, as well as primary, human macrophages. IL-1beta secretion was dependent on NLRP3, K+-efflux, TLR4, IRAK, Syk, caspase-1, caspase-8 and NADPH-oxidase. Importantly, while C. albicans induced robust IL-1beta release after 4 h, C. parapsilosis was not able to stimulate the production of IL-1beta 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-1beta production in response to a non-albicans Candida species, and these results enhance our understanding about the immune response against C. parapsilosis.
Physical Description:Terjedelem: 12 p-Azonosító: 43129
ISSN:2045-2322