Innate Error Immunities of the Th17 Immune Pathway Associated With Chronic Mucocutaneous Candidiasis: A Systematic Review

December 2023 | Volume 22 | Issue 12 | 1197 | Copyright © December 2023


Published online November 16, 2023

Verda S. Mirza DOa, Mallory L. Zaino MDb, Steven R. Feldman MD PhDb,c

aMarian University College of Osteopathic Medicine, Indianapolis, IN
bCenter for Dermatology Research, Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC
cDepartment of Pathology, Wake Forest School of Medicine, Winston-Salem, NC

Abstract
Background: Candida albicans is an opportunistic pathogenic yeast commensal in human mucosa. In individuals with compromised immune systems, it can present as chronic mucocutaneous candidiasis (CMC) or systemic infection. CMC often exists in the presence of other infectious phenotypes due to dysfunction of the Th17 immune response.
Objective: To examine innate error immunities (IEI) of the Th17 immune response associated with CMC.
Methods: MEDLINE PubMed, Embase, and Web of Science were searched for keywords and Medical Subject Headings (MeSH) related to the subject of interest. Nonapplicable and non-primary research methodologies were excluded.
Results: We identified 266 articles; 89 were removed for being a duplicate, 108 for irrelevance, and 51 for being a review. We examined 18 studies, 5 on murine models, and 13 human studies.
Conclusion: Case reports in patients with CMC have identified a range of mutations in IL-17F, IL-17RA, IL-17RC, and ACT1. Mouse models confirm the role of IL-17A and IL-17F in disease susceptibility.

J Drugs Dermatol. 2023;22(12):1197-1203. doi:10.36849/JDD.7579

INTRODUCTION

Candida albicans is an opportunistic pathogenic yeast that can cause thrush, intertrigo, and genital candidiasis. Individuals with compromised immune systems can present with chronic mucocutaneous candidiasis (CMC) or systemic infection.1-4

CMC is a chronic infection of the skin, nails, oropharyngeal, and genital mucosae classified as syndromic or CMC disease (CMCD).2 Syndromic CMC is CMC in addition to other infectious phenotypes. This includes autosomal-dominant (AD) hyper IgE syndrome (HIES), autosomal-recessive (AR) autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED/APS-1), and mutations in signal transducer and activator of transcription 1 (STAT1), interleukin (IL)-12 receptor β1 (IL-12Rβ1), IL-12p40, caspase recruitment domain-containing protein 9 (CARD9), or retinoic acid-related orphan receptor γT (RORγT). CMCD is CMC independent of other immune disorders.1-6


 Both types of CMC relate to the dysfunction of Th17 cells and their cytokines. Six cytokines (IL-17A-E) and 5 receptors (IL-17RA-RE) make up the IL-17 family. Important to the IL-17Rs is the ACT1 adapter molecule required for cell signaling. To date, there are 8 innate error immunities (IEI) in the IL-17 pathway: (1) IL-17A, (2) IL-17F, (3) IL-17AF, (4) IL-17C, (5) IL-17E (IL-25), (6) IL-17RA, (7) IL-17RC, and (8) ACT1/TRAF3 interacting protein 2 (TRAF3IP2).1-6

In this review, we examine each of the IEIs as relates to CMC.

MATERIALS AND METHODS

The search was developed in collaboration with a Wake Forest University Health Sciences librarian. It was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered on PROSPERO (CRD42022384733).
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