Cutting edge: Candida albicans hyphae formation triggers activation of the Nlrp3 inflammasome.
The proinflammatory cytokine IL-1beta plays an important role in antifungal immunity; however, the mechanisms by which fungal pathogens trigger IL-1beta secretion are unclear. In this study we show that infection with Candida albicans is sensed by the Nlrp3 inflammasome, resulting in the subsequent release of IL-1beta. The ability of C. albicans to switch from a unicellular yeast form into a filamentous form is essential for activation of the Nlrp3 inflammasome, as C. albicans mutants incapable of forming hyphae were defective in their ability to induce macrophage IL- 1beta secretion. Nlrp3-deficient mice also demonstrated increased susceptibility to infection with C. albicans, which is consistent with a key role for Nlrp3 in innate immune responses to the pathogen C. albicans.
Joly
Sophie
S
Division of Infectious Diseases, University of Iowa, Iowa City, IA 52242, USA.
Ma
Ning
N
Sadler
Jeffrey J
JJ
Soll
David R
DR
Cassel
Suzanne L
SL
Sutterwala
Fayyaz S
FS
D000818:Animals; D002176:Candida albicans / Q000166:cytology / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D025301:Hyphae / Q000276:immunology*; D007109:Immunity; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein
D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse
J Exp Med. 2006 Jun 12;203(6):1407-12
16717117
J Immunol. 2004 Mar 1;172(5):3059-69
14978111
J Bacteriol. 1987 Jan;169(1):189-97
3539914
Nature. 2006 Mar 9;440(7081):228-32
16407890
Immunity. 2009 Apr 17;30(4):566-75
19362023
Nature. 2009 May 21;459(7245):433-6
19339971
Nat Immunol. 2008 Aug;9(8):847-56
18604214
Immunity. 2006 Mar;24(3):317-27
16546100
Immunity. 2009 Apr 17;30(4):556-65
19362020
J Infect Dis. 2006 May 15;193(10):1419-26
16619190
Cell. 1997 Sep 5;90(5):939-49
9298905
J Immunol. 2009 Jan 15;182(2):1146-54
19124758
J Exp Med. 2009 Jan 16;206(1):79-87
19139171
J Clin Microbiol. 2004 Mar;42(3):1024-9
15004048
J Exp Med. 2000 May 15;191(10):1661-74
10811860
J Clin Microbiol. 1997 Sep;35(9):2348-58
9276415
Microbiology (Reading). 1997 Dec;143 ( Pt 12):3733-3746
9421899
Microbiology (Reading). 2002 Sep;148(Pt 9):2661-2674
12213913
Curr Opin Immunol. 2009 Feb;21(1):10-6
19223160
J Clin Microbiol. 1996 Dec;34(12):3063-71
8940449