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Review
. 2012 Dec;12(6):616-22.
doi: 10.1097/ACI.0b013e328358cc0b.

Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis

Anne Puel  1 , Sophie Cypowyj, László Maródi, Laurent Abel, Capucine Picard, Jean-Laurent Casanova
Affiliations
Review

Inborn errors of human IL-17 immunity underlie chronic mucocutaneous candidiasis

Anne Puel et al. Curr Opin Allergy Clin Immunol. 2012 Dec.

Abstract

Purpose of review: Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent symptomatic infection of the nails, skin and mucosae mostly by Candida albicans. CMC is common in patients with profound primary T-cell immunodeficiency, who often display multiple infectious and autoimmune diseases. Patients with syndromic CMC, including autosomal dominant hyper IgE syndrome (AD-HIES) and autosomal recessive autoimmune polyendocrinopathy syndrome type I (APS-I), display fewer other infections. Patients with isolated CMC (CMCD) rarely display any other severe disease. We review here recent progress in the genetic dissection of these three types of inherited CMC.

Recent findings: Low IL-17 T-cell proportions were reported in patients with AD-HIES bearing heterozygous STAT3 mutations, prone to CMC and staphylococcal diseases, and in a kindred with autosomal recessive CARD9 deficiency, prone to CMC and other fungal infections. High levels of neutralizing autoantibodies against IL-17 cytokines were documented in patients with APS-I presenting with CMC as their only infectious disease. The first three genetic causes of CMCD were then reported: autosomal recessive IL-17RA and autosomal dominant IL-17F deficiencies and autosomal dominant STAT1 gain-of-function, impairing IL-17-producing T-cell development.

Summary: Inborn errors of human IL-17 immunity underlie CMC. Impaired IL-17 immunity may therefore account for CMC in other settings, including patients with acquired immunodeficiency.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1. Inborn errors of IL-17 immunity underlie chronic mucocutaneous candidiasis
Schematic representation of IL-17 mediated immunity with the cooperation between cells recognizing C. albicans (phagocytes and epithelial cells) and IL-17 cytokine producing cells (T and innate lymphocytes). Upon C. albicans recognition by PRRs (pathogen recognition receptors, including Dectin-1, Dectin-2, or Mincle), the adaptor molecule CARD9 mediates the induction of pro-inflammatory cytokines by myeloid or epithelial cells, such as IL-1β, IL-6 and IL-23. Upon binding to their receptors expressed on T and innate lymphocytes, pro-inflammatory cytokines, such as IL-6 or IL-23, activate T lymphocytes via the transcription factor STAT3 resulting in their differentiation into IL-17-producing T cells. Patients with AR CARD9 deficiency (pink), AD STAT3 deficiency (pink), or AR AIRE deficiency (not represented here) with high levels of neutralizing autoantibodies against IL-17A, IL-17F and/or IL-22 (pink), suffer from syndromic CMC and display impaired IL-17 mediated immunity. Patients with AR IL-17RA or AD IL-17F deficiency and impaired IL-17 response or function, respectively, or with AD STAT1 gain-of-function and impaired development of IL-17 producing T cells suffer from CMCD (in blue).
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