Aspergillus fumigatus conidial melanin modulates host cytokine response.
Melanin biopigments have been linked to fungal virulence. Aspergillus fumigatus conidia are melanised and are weakly immunogenic. We show that melanin pigments on the surface of resting Aspergillus fumigatus conidia may serve to mask pathogen-associated molecular patterns (PAMPs)-induced cytokine response. The albino conidia induced significantly more proinflammatory cytokines in human peripheral blood mononuclear cells (PBMC), as compared to melanised wild-type conidia. Blocking dectin-1 receptor, Toll-like receptor 4 or mannose receptor decreased cytokine production induced by the albino but not by the wild type conidia. Moreover, albino conidia stimulated less potently, cytokine production in PBMC isolated from an individual with defective dectin-1, compared to the stimulation of cells isolated from healthy donors. These results suggest that β-glucans, but also other stimulatory PAMPs like mannan derivatives, are exposed on conidial surface in the absence of melanin. Melanin may play a modulatory role by impeding the capability of host immune cells to respond to specific ligands on A. fumigatus.
Chai
Louis Y A
LY
Department of Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, Geert Grootplein 8, 6525 GA, Nijmegen, The Netherlands.
Netea
Mihai G
MG
Sugui
Janyce
J
Vonk
Alieke G
AG
van de Sande
Wendy W J
WW
Warris
Adilia
A
Kwon-Chung
Kyung J
KJ
Kullberg
Bart Jan
BJ
D001228:Aspergillosis / Q000276:immunology* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000276:immunology* / Q000472:pathogenicity*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D054884:Host-Pathogen Interactions; D006801:Humans; D007963:Leukocytes, Mononuclear; D008543:Melanins / Q000276:immunology*; D013172:Spores, Fungal / Q000276:immunology*; D014774:Virulence
D016207:Cytokines; D008543:Melanins