IL-17 and infections.
IL-17 immunity has been shown to be essential for mucocutaneous protection against Candida albicans in mice and humans. However, mice with defective IL-17 immunity display broader susceptibility, as they are also prone to infections with diverse infectious agents at various sites. Humans with genetic defects affecting their IL-17 immunity usually suffer from chronic mucocutaneous candidiasis (CMC): recurrent or persistent infections of the skin, nails, and mucosae with C. albicans, with or without other clinical signs. Most patients with autosomal dominant (AD) hyper-IgE syndrome (HIES) due to STAT3 deficiency or AD STAT1 gain-of-function display impaired IL-17-producing T-cell development, and CMC is one of their principal clinical manifestations. Similarly, patients with autosomal recessive (AR) autoimmune polyendocrine syndrome type 1 (APS-1) caused by AIRE deficiency have high levels of neutralizing autoantibodies against IL-17A, IL-17F and/or IL-22 and present CMC as their only infectious disease. Finally, CMC is the main clinical phenotype observed in patients with inborn errors specifically affecting IL-17 immunity. Indeed, patients with AD IL-17F deficiency or AR IL-17RA or ACT1 deficiency display CMC and, to a lesser extent, superficial staphylococcal diseases. Candida infection was recently reported in psoriasis patients treated with anti-IL-17A antibodies. Careful monitoring for CMC is thus important during anti-IL-17 treatment.
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM 1163, Paris, France; Imagine Institute, University Paris Descartes, Paris, France.
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Ling
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM 1163, Paris, France; Imagine Institute, University Paris Descartes, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, the Rockefeller University, New York, NY, USA. Electronic address: anne.puel@inserm.fr.
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Puel
D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D002178:Candidiasis, Chronic Mucocutaneous / Q000209:etiology / Q000276:immunology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000150:complications; D007239:Infections / Q000276:immunology*; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*; D007589:Job Syndrome / Q000150:complications / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D016884:Polyendocrinopathies, Autoimmune / Q000150:complications / Q000235:genetics / Q000276:immunology; D011565:Psoriasis / Q000150:complications / Q000188:drug therapy / Q000276:immunology; D013207:Staphylococcal Skin Infections / Q000276:immunology
D000911:Antibodies, Monoclonal; D020381:Interleukin-17
Candidiasis mucocutánea crónica; Chronic mucocutaneous candidiasis; Errores innatos de la inmunidad IL-17; IL-17; Inborn errors of IL-17 immunity; Inmunodeficiencias primarias; Primary immunodeficiencies