Candida albicans modulates host defense by biosynthesizing the pro-resolving mediator resolvin E1.
Candida albicans is an opportunistic fungal pathogen of humans that resides commensally on epithelial surfaces, but can cause inflammation when pathogenic. Resolvins are a class of anti-inflammatory lipids derived from omega-3 polyunsaturated fatty acids (PUFA) that attenuate neutrophil migration during the resolution phase of inflammation. In this report we demonstrate that C. albicans biosynthesizes resolvins that are chemically identical to those produced by human cells. In contrast to the trans-cellular biosynthesis of human Resolvin E1 (RvE1), RvE1 biosynthesis in C. albicans occurs in the absence of other cellular partners. C. albicans biosynthesis of RvE1 is sensitive to lipoxygenase and cytochrome P450 monoxygenase inhibitors. We show that 10nM RvE1 reduces neutrophil chemotaxis in response to IL-8; 1nM RvE1 enhanced phagocytosis of Candida by human neutrophils, as well as intracellular ROS generation and killing, while having no direct affect on neutrophil motility. In a mouse model of systemic candidiasis, RvE1 stimulated clearance of the fungus from circulating blood. These results reveal an inter-species chemical signaling system that modulates host immune functions and may play a role in balancing host carriage of commensal and pathogenic C. albicans.
Haas-Stapleton
Eric J
EJ
Department of Cell and Tissue Biology, University of California at San Francisco, San Francisco, California, United States of America.
Lu
Yan
Y
Hong
Song
S
Arita
Makoto
M
Favoreto
Silvio
S
Nigam
Santosh
S
Serhan
Charles N
CN
Agabian
Nina
N
D000818:Animals; D002176:Candida albicans / Q000472:pathogenicity / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D002853:Chromatography, Liquid; D004281:Docosahexaenoic Acids / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis; D053719:Tandem Mass Spectrometry; D014774:Virulence
D016209:Interleukin-8; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid