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The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes
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The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes
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Journal Article
The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes
2018
Overview
Clearance of invading microbes requires phagocytes of the innate immune system. However, successful pathogens have evolved sophisticated strategies to evade immune killing. The opportunistic human fungal pathogen
Candida albicans
is efficiently phagocytosed by macrophages, but causes inflammasome activation, host cytolysis, and escapes after hypha formation. Previous studies suggest that macrophage lysis by
C
.
albicans
results from early inflammasome-dependent cell death (pyroptosis), late damage due to glucose depletion and membrane piercing by growing hyphae. Here we show that Candidalysin, a cytolytic peptide toxin encoded by the hypha-associated gene
ECE1
, is both a central trigger for NLRP3 inflammasome-dependent caspase-1 activation via potassium efflux and a key driver of inflammasome-independent cytolysis of macrophages and dendritic cells upon infection with
C
.
albicans
. This suggests that Candidalysin-induced cell damage is a third mechanism of
C
.
albicans
-mediated mononuclear phagocyte cell death in addition to damage caused by pyroptosis and the growth of glucose-consuming hyphae.
Phagocytic cells of the innate immune system play critical roles in defence against invading pathogens including the opportunistic pathogen
Candida albicans
. Here the authors show that
C
.
albicans
derived Candidalysin in addition to being a cell-damaging toxin to mononuclear phagocytes is a trigger of NLRP3 inflammasome activation in these cells.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/21
/ 14/63
/ 64/60
/ Animals
/ Bone Marrow Cells - drug effects
/ Bone Marrow Cells - metabolism
/ Dendritic Cells - drug effects
/ Dendritic Cells - metabolism
/ Efflux
/ Female
/ Fungi
/ Glucose
/ Humanities and Social Sciences
/ Humans
/ Hyphae
/ Interleukin-1beta - metabolism
/ Leukocytes, Mononuclear - cytology
/ Leukocytes, Mononuclear - drug effects
/ Leukocytes, Mononuclear - metabolism
/ Lysis
/ Necrosis
/ NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
/ Science
/ Toxins
