Inborn errors of mucocutaneous immunity to Candida albicans in humans: a role for IL-17 cytokines?
The various clinical manifestations of chronic mucocutaneous candidiasis (CMC) often result from acquired T-cell immunodeficiencies. More rarely, CMC results from inborn errors of immunity, the recent dissection of which has shed light on the molecular mechanisms of mucocutaneous immunity to Candida albicans. CMC may accompany various other infectious diseases in patients with almost any broad and profound T-cell primary immunodeficiency. By contrast, CMC is one of the few key infections in patients with autosomal dominant hyper IgE syndrome (mutations in STAT3), and in rare patients with autosomal recessive predisposition to mucocutaneous and invasive fungal infections (mutation in CARD9). In patients with mutations in STAT3 and CARD9, the development of IL-17-producing T cells is impaired. Moreover, CMC is the principal, if not only, infection in patients with autosomal recessive autoimmune polyendocrinopathy syndrome-I (mutations in AIRE). Patients with this condition have high titers of neutralizing autoantibodies (auto-Abs) against the IL-17 cytokines IL-17A, IL-17F, and IL-22. Collectively, these data suggest that human IL-17A, IL-17F, and IL-22 are essential for mucocutaneous immunity to C. albicans. They also suggest that the distinct syndrome of isolated CMC, without auto-immunity or other infections, may be caused by inborn errors of IL-17 immunity.
Puel
Anne
A
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Inserm U980, University Paris Descartes, Necker Medical School, Paris, France, EU. anne.puel@inserm.fr
Picard
Capucine
C
Cypowyj
Sophie
S
Lilic
Desa
D
Abel
Laurent
L
Casanova
Jean-Laurent
JL
D002176:Candida albicans / Q000276:immunology*; D002178:Candidiasis, Chronic Mucocutaneous / Q000276:immunology*; D030342:Genetic Diseases, Inborn / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000235:genetics*; D020381:Interleukin-17 / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D020381:Interleukin-17