Candida albicans releases soluble factors that potentiate cytokine production by human cells through a protease-activated receptor 1- and 2-independent pathway.
The innate immune system recognizes pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRR) and transduces downstream signaling to activate the host defense. Here we report that in addition to direct PAMP-PRR interactions, live Candida albicans cells can release soluble factors to actively potentiate interleukin-6 (IL-6) and IL-8 production induced in human mononuclear cells by the fungi. Although protease-activated receptor 1 (PAR1) and PAR2 ligation can moderately upregulate Toll-like receptor 4 (TLR4)-mediated IL-8 production, no effect on the C. albicans-induced cytokine was apparent. Similarly, the blockade of PAR signaling did not reverse the potentiation of cytokine production induced by soluble factors released by C. albicans. In conclusion, C. albicans releases soluble factors that potentiate cytokine release in a PAR1/2-independent manner. Thus, human PAR1 and PAR2 have a redundant role in the activation of human cells by C. albicans.
Department of Medicine, Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, The Netherlands.
Shih-Chin
SC
Cheng
Louis Y A
LY
Chai
Leo A B
LA
Joosten
Anna
A
Vecchiarelli
Bernhard
B
Hube
Jos W
JW
Van Der Meer
Bart Jan
BJ
Kullberg
Mihai G
MG
Netea
D002176:Candida albicans / Q000378:metabolism*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000235:genetics / Q000378:metabolism*
D017077:Culture Media, Conditioned; D016207:Cytokines; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2