title: 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-1β (IL-1β) secretion in THP-1, as well as primary, human macrophages. IL-1β secretion was dependent on NLRP3, K+-efflux, TLR4, IRAK, Syk, caspase-1, caspase-8 and NADPH-oxidase. Importantly, while C. albicans induced robust IL-1β release after 4 h, C. parapsilosis was not able to stimulate the production of IL-1β 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-1β production in response to a non-albicans Candida species, and these results enhance our understanding about the immune response against C. parapsilosis.
authors.affiliation: Department of Microbiology, University of Szeged, Szeged, Hungary.
authors.forename: Adél
authors.initials: A
authors.lastname: Tóth
authors.affiliation: Department of Microbiology, University of Szeged, Szeged, Hungary.
authors.forename: Erik
authors.initials: E
authors.lastname: Zajta
authors.affiliation: Department of Microbiology, University of Szeged, Szeged, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Csonka
authors.affiliation: Department of Microbiology, University of Szeged, Szeged, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Vágvölgyi
authors.affiliation: Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Microbiology, University of Szeged, Szeged, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Gácser
mesh_terms: D002176:Candida albicans / Q000276:immunology; D000074429:Candida parapsilosis / Q000276:immunology*; D020170:Caspase 1 / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D002401:Cathepsin B; D020170:Caspase 1