Lessons from the inflammasome: a molecular sentry linking Candida and Crohn's disease.
Candida albicans is a diploid fungus that colonizes the gastrointestinal tract asymptomatically in a large proportion of the human population, but can cause life-threatening conditions in immunocompromised patients. Recent immunological investigations have revealed the Nod-like receptor pyrin domain-containing protein 3 (NLRP3) to be a cytosolic surveillance mechanism against germinating Candida. These observations point to the idea of a molecular link between Candida and a spectrum of auto-inflammatory diseases. When excessive activation of NLRP3 occurs, it can confer resistance against disseminating Candida infection but might also cause NLRP3-associated periodic syndromes. Alternatively, we propose a pathophysiological model whereby a defective NLRP3-coupled inflammasome can result in enhanced mucosal colonization of granuloma-provoking microorganisms, including C. albicans, precipitating the formation of Crohn's disease-associated inflammatory lesions.
University of British Columbia, Centre for Microbial Disease & Immunity Research, 2259 Lower Mall, Vancouver, BC, Canada V6T 1Z4.
Linda M
LM
Rehaume
Thierry
T
Jouault
Mathias
M
Chamaillard
D000818:Animals; D002175:Candida / Q000276:immunology*; D002177:Candidiasis / Q000150:complications / Q000276:immunology*; D003424:Crohn Disease / Q000150:complications / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D006801:Humans; D007113:Immunity, Innate