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

Amy G Hise, Jeffrey Tomalka, Sandhya Ganesan, Krupen Patel, Brian A Hall, Gordon D Brown, Katherine A Fitzgerald

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352 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)487-497
Number of pages11
JournalCell Host & Microbe
Volume5
Issue number5
DOIs
Publication statusPublished - 21 May 2009

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Keywords

  • animals
  • Candida albicans
  • candidiasis
  • carrier proteins
  • caspase 1
  • cells, cultured
  • disease models, animal
  • female
  • host-pathogen interactions
  • humans
  • interleukin-1beta
  • leukocytes, mononuclear
  • macrophages
  • mice
  • mice, inbred C57BL
  • molimmuno
  • microbio

Cite this

Hise, A. G., Tomalka, J., Ganesan, S., Patel, K., Hall, B. A., Brown, G. D., & Fitzgerald, K. A. (2009). An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell Host & Microbe, 5(5), 487-497. https://doi.org/10.1016/j.chom.2009.05.002