Chronic Mucocutaneous Candidiasis in Humans with Inborn Errors of Interleukin-17 Immunity

• Published in: Science (American Association for the Advancement of Science) Vol. 332; no. 6025; pp. 65 - 68
• Main Authors: Puel, Anne, Cypowyj, Sophie, Bustamante, Jacinta, Wright, Jill F., Liu, Luyan, Lim, Hye Kyung, Migaud, Mélanie, Israel, Laura, Chrabieh, Maya, Audry, Magali, Gumbleton, Matthew, Toulon, Antoine, Bodemer, Christine, El-Baghdadi, Jamila, Whitters, Matthew, Paradis, Theresa, Brooks, Jonathan, Collins, Mary, Wolfman, Neil M., Al-Muhsen, Saleh, Galicchio, Miguel, Abel, Laurent, Picard, Capucine, Casanova, Jean-Laurent
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 01-04-2011; The American Association for the Advancement of Science
• Subjects: Alleles; Bacterial diseases; Biological and medical sciences; Candida; Candida albicans; Candidiasis, Chronic Mucocutaneous - genetics; Candidiasis, Chronic Mucocutaneous - immunology; Child; Child, Preschool; Cytokines; Female; Fibroblasts; Fungal infections; Genes, Dominant; Genes, Recessive; Genetic mutation; Genetics; Human; Human bacterial diseases; Human genetics; Humans; Immunity; Immunology; Infections; Infectious diseases; Innate immunity; Interleukin-17 - immunology; Male; Medical sciences; Molecular Sequence Data; Mucous membrane; Mutation; Nails; Pedigree; Receptors; Receptors, Interleukin-17 - genetics; Signal Transduction - genetics; Staphylococcal infections, streptococcal infections, pneumococcal infections; Staphylococcus aureus; Staphylococcus infections; T lymphocytes; Th17 Cells - immunology; Autoimmunity; Candida albicans; Candidiasis; Relapse; Mycosis; Activity; Autoimmune disease; Cellular immunity; Heterodimer; Fungi; Nail(anatomy); Partial; Etiology; Bacteria; Micrococcales; Genetics; Micrococcaceae; Dominant character; Mucocutaneous; Fungi Imperfecti; Staphylococcus aureus; Biological receptor; Human; Chronic disease; Deficiency; Genital system; Cytokine; Oral administration; Error; Recurrent; Interleukin 17; Genetic disease; Infection; Chronic; Autosomal character; Persistent infection; Bacteriosis; Recessive character; Skin; Staphylococcal infection
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1200439

Chronic mucocutaneous candidiasis disease (CMCD) is characterized by recurrent or persistent infections of the skin, nails, and oral and genital mucosae caused by Candida albicans and, to a lesser extent, Staphylococcus aureus, in patients with no other infectious or autoimmune manifestations. We report two genetic etiologies of CMCD: autosomal recessive deficiency in the cytokine receptor, interleukin-17 receptor A (IL-17RA), and autosomal dominant deficiency of the cytokine interleukin-17F (IL-17F). IL-17RA deficiency is complete, abolishing cellular responses to IL-17A and IL-17F homo- and heterodimers. By contrast, IL-17F deficiency is partial, with mutant IL-17F—containing homo- and heterodimers displaying impaired, but not abolished, activity. These experiments of nature indicate that human IL-17A and IL-17F are essential for mucocutaneous immunity against C. albicans, but otherwise largely redundant.