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

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.

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References
1.
Cho J, Pietras E, Garcia N, Ramos R, Farzam D, Monroe H . IL-17 is essential for host defense against cutaneous Staphylococcus aureus infection in mice. J Clin Invest. 2010; 120(5):1762-73. PMC: 2860944. DOI: 10.1172/JCI40891. View

2.
Ishigame H, Kakuta S, Nagai T, Kadoki M, Nambu A, Komiyama Y . Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity. 2009; 30(1):108-19. DOI: 10.1016/j.immuni.2008.11.009. View

3.
Minegishi Y, Saito M, Nagasawa M, Takada H, Hara T, Tsuchiya S . Molecular explanation for the contradiction between systemic Th17 defect and localized bacterial infection in hyper-IgE syndrome. J Exp Med. 2009; 206(6):1291-301. PMC: 2715068. DOI: 10.1084/jem.20082767. View

4.
Puel A, Doffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C . Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med. 2010; 207(2):291-7. PMC: 2822614. DOI: 10.1084/jem.20091983. View

5.
Wolk K, Witte E, Witte K, Warszawska K, Sabat R . Biology of interleukin-22. Semin Immunopathol. 2010; 32(1):17-31. DOI: 10.1007/s00281-009-0188-x. View