Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity

  • Science. 2011 Apr 1;332(6025):65-8. doi: 10.1126/science.1200439.
Anne Puel  1 ,  Sophie Cypowyj ,  Jacinta Bustamante ,  Jill F Wright ,  Luyan Liu ,  Hye Kyung Lim ,  Mélanie Migaud ,  Laura Israel ,  Maya Chrabieh ,  Magali Audry ,  Matthew Gumbleton ,  Antoine Toulon ,  Christine Bodemer ,  Jamila El-Baghdadi ,  Matthew Whitters ,  Theresa Paradis ,  Jonathan Brooks ,  Mary Collins ,  Neil M Wolfman ,  Saleh Al-Muhsen ,  Miguel Galicchio ,  Laurent Abel ,  Capucine Picard ,  Jean-Laurent Casanova
Affiliations
  • 1. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale, U980, and University Paris Descartes, Necker Medical School, 75015 Paris, France. [email protected]
PMID: 21350122 DOI: 10.1126/science.1200439
Abstract

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.