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

By A. Puel, Sophie Cypowyj, J. Bustamante, Jill F. Wright, Luyan Liu, H. Lim, M. Migaud, L. Israel, Maya Chrabieh, Magali Audry and 14 more. Science, 2011

1,019 citations recorded by the source corpus.

Chronic yeast infections in the absence of other infections result from genetic deficiencies in proinflammatory host responses. 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.

Subfields: Immunology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/79076f4eda18da1a83cc0fdd6d92e8993b8598f5

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. D. Cua
2. Bali Pulendran
3. C. Tato
4. Rafi Ahmed
5. T. Mcclanahan
6. W. Blumenschein
7. Yi Chen
8. J. Krueger

In Infectious Diseases

1. Rafi Ahmed
2. Bali Pulendran

Citations in the corpus

• IL-23-Independent IL-17 Production Regulates Intestinal Epithelial Permeability (2015, positive): “IL-17 contributes to defense against the gram-negative pathogens Klebsiella pneumonia and Citrobacter rodentium as well as having an essential role in mucocutaneous immunity against Candida albicans (Puel et al., 2011).”
• Psoriasis Pathogenesis and the Development of Novel, Targeted Immune Therapies (2017, positive): “The association of IL-17 blockade with Candida infections likely reflects the normal role for this cytokine in the innate immune response against this organism; therefore its absence renders the skin susceptible to overgrowth in the skin and mucosal tissues, as observed in patients with inborn error”
• Candida albicans morphogenesis and host defence: discriminating invasion from colonization (2011, neutral): “Moreover, a recent report identified genetic defects in IL-17R and in IL-17F in some patients with CM”
• Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis (2011, background): “In a consanguineous family from Morocco, a child with CMCD was found to display AR complete IL-17RA deficiency (Puel et al., 2011).”
• Immunological mechanisms of vaccination (2011, background): “Finally, humans with particular mutations in the genes encoding IL-17 or its receptor have chronic mucocutaneous immunity to Candida albicans”