Human dectin-1 deficiency and mucocutaneous fungal infections.
Mucocutaneous fungal infections are typically found in patients who have no known immune defects. We describe a family in which four women who were affected by either recurrent vulvovaginal candidiasis or onychomycosis had the early-stop-codon mutation Tyr238X in the beta-glucan receptor dectin-1. The mutated form of dectin-1 was poorly expressed, did not mediate beta-glucan binding, and led to defective production of cytokines (interleukin-17, tumor necrosis factor, and interleukin-6) after stimulation with beta-glucan or Candida albicans. In contrast, fungal phagocytosis and fungal killing were normal in the patients, explaining why dectin-1 deficiency was not associated with invasive fungal infections and highlighting the specific role of dectin-1 in human mucosal antifungal defense.
Department of Internal Medicine and the Nijmegen Institute for Infection, Inflammation, and Immunity, Radboud University Nijmegen, Nijmegen, The Netherlands.
Bart
B
Ferwerda
Gerben
G
Ferwerda
Theo S
TS
Plantinga
Janet A
JA
Willment
Annemiek B
AB
van Spriel
Hanka
H
Venselaar
Clara C
CC
Elbers
Melissa D
MD
Johnson
Alessandra
A
Cambi
Cristal
C
Huysamen
Liesbeth
L
Jacobs
Trees
T
Jansen
Karlijn
K
Verheijen
Laury
L
Masthoff
Servaas A
SA
Morré
Gert
G
Vriend
David L
DL
Williams
John R
JR
Perfect
Leo A B
LA
Joosten
Cisca
C
Wijmenga
Jos W M
JW
van der Meer
Gosse J
GJ
Adema
Bart Jan
BJ
Kullberg
Gordon D
GD
Brown
Mihai G
MG
Netea
D000818:Animals; D002176:Candida albicans / Q000276:immunology; D002177:Candidiasis / Q000235:genetics* / Q000276:immunology; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics; D002181:Candidiasis, Vulvovaginal / Q000235:genetics; D018389:Codon, Nonsense; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D037181:Lectins, C-Type; D008297:Male; D008322:Mammals / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D014009:Onychomycosis / Q000235:genetics*; D010375:Pedigree; D000099181:Dectin-1
D018389:Codon, Nonsense; D016207:Cytokines; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000099181:Dectin-1