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Review
. 2023 Jun;11(6):1624-1634.
doi: 10.1016/j.jaip.2023.04.015. Epub 2023 Apr 26.

The Th17/IL-17 Axis and Host Defense Against Fungal Infections

Stuart G Tangye  1 , Anne Puel  2
Affiliations
Review

The Th17/IL-17 Axis and Host Defense Against Fungal Infections

Stuart G Tangye et al. J Allergy Clin Immunol Pract. 2023 Jun.

Abstract

Chronic mucocutaneous candidiasis (CMC) was recognized as a primary immunodeficiency in the early 1970s. However, for almost 40 years, its genetic etiology remained unknown. The progressive molecular and cellular description of inborn errors of immunity (IEI) with syndromic CMC pointed toward a possible role of IL-17-mediated immunity in protecting against fungal infection and CMC. Since 2011, novel IEI affecting either the response to or production of IL-17A and/or IL-17F (IL-17A/F) in patients with isolated or syndromic CMC provided formal proof of the pivotal role of the IL-17 axis in mucocutaneous immunity to Candida spp, and, to a lesser extent, to Staphylococcus aureus in humans. In contrast, IL-17-mediated immunity seems largely redundant against other common microbes in humans. In this review, we outline the current knowledge of IEI associated with impaired IL-17A/F-mediated immunity, highlighting our current understanding of the role of IL-17A/F in human immunity.

Keywords: Anticytokine autoantibodies; Antifungal immunity; Chronic mucocutaneous candidiasis; IL-17 cytokines; Inborn errors of immunity; STATs; Th17 cells.

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Conflict of interest statement

Conflict of interest: the authors have no conflicts to declare

Figures

Figure 1:
Figure 1:. Inborn errors of immunity and phenocopies that disrupt IL-17-mediated immunity against fungal infections.
In response to cytokines produced by myeloid cells, naïve CD4+ T cells differentiate into specialised subsets of effectors cells. Production of canonical cytokines enables elicitation of specific effector functions important for host defence against pathogen infections. In the setting of Th17 cells, integration of STAT3/ZNF341-dependent signals downstream of cytokines including IL-23 and IL-21 in CD4+ T cells leads to expression of the transcription factor RORγt and induction of the Th17 program. IL-17 cytokines activate epithelial cells via IL-17R/ACT1/JNK1, resulting in production of pro-inflammatory and anti-microbial peptides. Molecules shown in red have been found to be mutated in specific IEI and impair either the generation or function of Th17 cells causing CMC (and often Staph infection). Autoantibodies against IL-17A/IL-17F phenocopy inborn errors of IL-17-mediated immunity.
See this image and copyright information in PMC

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