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Updated: Nov 24, 2025
Th17 Inflammation Model of Oropharyngeal Candidiasis in Immunodeficient Mice
Published on: February 18, 2015
Two patients with chronic mucocutaneous candidiasis caused by TRAF3IP2 deficiency
Samantha Shafer1, Yikun Yao1, William Comrie1
1Molecular Development of the Immune System Section, Laboratory of Immune System Biology, and Clinical Genomics Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
Background:
TRAF3 interacting protein 2 (TRAF3IP2) (Act1) is an adapter protein that interacts with IL-17R via its similar expression to fibroblast growth factor genes and IL-17R domain and coordinates 2 separate proinflammatory pathways following IL-17 cytokine stimulation.
Objective:
We sought to elucidate the immunologic consequences of TRAF3IP2 homozygous mutations to improve treatments for immunodeficiency patients with chronic mucocutaneous candidiasis.
Methods:
We describe 2 patients presenting with chronic mucocutaneous candidiasis who harbor biallelic nonsense mutations in TRAF3IP2. The cellular and molecular features of this genetic defect were assessed using in vitro cytokine assays and protein analysis.
Results:
We show that the homozygous mutation causes complete loss of protein expression. We also show that the absence of TRAF3IP2 was associated with a defective response to combined IL-2/IL-25 (IL-17E) stimulation.
Conclusions:
Failure to initiate normal signaling downstream of IL-17R engagement likely contributes to the patients' recurrent fungal infections. These findings add to our molecular understanding of genetic defects affecting this critical pathway of antifungal immunity.
Insights
Homozygous mutations in TRAF3IP2 (Act1) cause loss of protein expression, leading to defective antifungal immunity and chronic mucocutaneous candidiasis in patients. This highlights TRAF3IP2
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- TRAF3IP2 (Act1) is an adapter protein crucial for IL-17R signaling and proinflammatory pathways.
- IL-17R signaling is vital for coordinating immune responses against fungal infections.
Observation:
- Two patients with chronic mucocutaneous candidiasis presented with biallelic nonsense mutations in TRAF3IP2.
- These mutations resulted in a complete loss of TRAF3IP2 protein expression.
Findings:
- Absence of TRAF3IP2 impaired the response to combined IL-2/IL-25 (IL-17E) stimulation.
- Defective IL-17R signaling downstream of TRAF3IP2 contributes to recurrent fungal infections.
Implications:
- Elucidating TRAF3IP2's role deepens understanding of genetic defects in antifungal immunity.
- Findings may inform improved treatments for immunodeficiency patients with chronic mucocutaneous candidiasis.
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