title: New host defense mechanisms against Candida species clarify the basis of clinical phenotypes.
abstract: Chronic Candida species infection of the skin and mucosal membranes is viewed as a group of disorders all sharing a similar clinical condition, the susceptibility to localized fungal infections, which can be isolated or as a feature associated with various other entities. Although the pathogenesis underlying such a tendency had previously been poorly understood, the last decade has witnessed significant progress in revealing the molecular and immunologic mechanisms involved in antifungal immunity. T(H)17 cells and their specific cytokines (IL-17A and IL-17F cytokines and IL-22) are the main players in conferring antifungal protection. Autoimmune polyendocrinopathy and ectodermal dystrophy and hyper-IgE syndrome are 2 entities caused by different genetic mutations affecting distinct immune pathways but eventually share a similar clinical phenotype of Candida species infection. Impaired T(H)17 responses, although mediated by different mechanisms, seem to underlie this common feature: neutralizing autoantibodies against IL-17A and 1L-22 are involved in patients with autoimmune polyendocrinopathy and ectodermal dystrophy syndrome, whereas abnormal T(H)17 proliferation and IL-17 production are observed in the latter. Although various degrees of T(H)17 dysfunction were also observed in most cases of isolated chronic mucocutaneous candidiasis, only in very few families was a distinct mutation detected (caspase recruitment domain family, member 9 [CARD9]), thus indicating certain forms of chronic mucocutaneous candidiasis as monogenic with a Mendelian pattern of inheritance. Hopefully, these data will open the way for further searches for other genes and for introducing new treatment modalities.
authors.affiliation: Pediatric Immunology Unit, Meyer's Children's Hospital, Rappaport Medical Faculty, Technion, Haifa, Israel.
authors.forename: Suheir
authors.initials: S
authors.lastname: Hanna
authors.forename: Amos
authors.initials: A
authors.lastname: Etzioni
authors.forename: Amos
authors.initials: A
authors.lastname: Etzoni
mesh_terms: D002175:Candida / Q000276:immunology; D002177:Candidiasis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D002178:Candidiasis, Chronic Mucocutaneous / Q000209:etiology / Q000235:genetics / Q000276:immunology; D004198:Disease Susceptibility; D005799:Genes, Dominant; D006801:Humans; D007113:Immunity, Innate; D053762:Interleukin-12 Subunit p40 / Q000172:deficiency / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis; D007589:Job Syndrome / Q000150:complications / Q000235:genetics / Q000276:immunology; D009154:Mutation; D010641:Phenotype; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications / Q000235:genetics / Q000276:immunology; D053707:Receptors, Interleukin-12 / Q000172:deficiency / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics; D058504:Th17 Cells / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D000096927:AIRE Protein
chemical_list: D053762:Interleukin-12 Subunit p40; D020381:Interleukin-17; D053707:Receptors, Interleukin-12; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D000096927:AIRE Protein; C508438:IL12RB1 protein, human; C494086:STAT3 protein, human