Format

Send to

Choose Destination
See comment in PubMed Commons below
Cell Host Microbe. 2009 May 8;5(5):487-97. doi: 10.1016/j.chom.2009.05.002.

An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans.

Author information

1
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106, USA. amy.hise@case.edu

Abstract

Candida albicans is an opportunistic fungal pathogen causing life-threatening mucosal and systemic infections in immunocompromised humans. Using a murine model of mucosal Candida infection, we investigated the role of the proinflammatory cytokine IL-1beta in host defense to Candida albicans. We find that the synthesis, processing, and release of IL-1beta in response to Candida are tightly controlled and first require transcriptional induction, followed by a second signal leading to caspase-1-mediated cleavage of the pro-IL-1beta cytokine. The known fungal pattern recognition receptors TLR2 and Dectin-1 regulate IL-1beta gene transcription, whereas the NLRP3-containing proinflammatory multiprotein complex, the NLRP3 inflammasome, controls caspase-1-mediated cleavage of pro-IL-1beta. Furthermore, we show that TLR2, Dectin-1, and NLRP3 are essential for defense against dissemination of mucosal infection and mortality in vivo. Therefore, in addition to sensing bacterial and viral pathogens, the NLRP3 inflammasome senses fungal pathogens and is critical in host defense against Candida.

PMID:
19454352
PMCID:
PMC2824856
DOI:
10.1016/j.chom.2009.05.002
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center