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Updated: Jun 22, 2025
Th17 Inflammation Model of Oropharyngeal Candidiasis in Immunodeficient Mice
Published on: February 18, 2015
Combinatorial actions of IL-22 and IL-17 drive optimal immunity to oral candidiasis through SPRRs
Felix E Y Aggor1, Martinna Bertolini1,2, Bianca M Coleman1
1University of Pittsburgh, Division of Rheumatology and Clinical Immunology, Pittsburgh, Pennsylvania, United States of America.
Abstract:
Oropharyngeal candidiasis (OPC) is the most common human fungal infection, arising typically from T cell immune impairments. IL-17 and IL-22 contribute individually to OPC responses, but here we demonstrate that the combined actions of both cytokines are essential for resistance to OPC. Mice lacking IL-17RA and IL-22RA1 exhibited high fungal loads in esophagus- and intestinal tract, severe weight loss, and symptoms of colitis. Ultimately, mice succumbed to infection. Dual loss of IL-17RA and IL-22RA impaired expression of small proline rich proteins (SPRRs), a class of antimicrobial effectors not previously linked to fungal immunity. Sprr2a1 exhibited direct candidacidal activity in vitro, and Sprr1-3a-/- mice were susceptible to OPC. Thus, cooperative actions of Type 17 cytokines mediate oral mucosal anti-Candida defenses and reveal a role for SPRRs.
Insights
The combined action of IL-17 and IL-22 cytokines is crucial for fighting oropharyngeal candidiasis (OPC). This study reveals small proline-rich proteins (SPRRs) as key antifungal effectors in mucosal immunity.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Oropharyngeal candidiasis (OPC) is a common fungal infection, often linked to T cell deficiencies.
- Interleukin-17 (IL-17) and Interleukin-22 (IL-22) are known to play roles in OPC, but their combined effect is not fully understood.
Purpose of the Study:
- To investigate the essential role of combined IL-17 and IL-22 signaling in host defense against OPC.
- To identify novel molecular mechanisms and effector molecules involved in anti-Candida immunity.
Main Methods:
- Utilized knockout mouse models lacking IL-17 receptor A (IL-17RA) and IL-22 receptor 1 (IL-22RA1) to assess susceptibility to OPC.
- Analyzed fungal loads, host weight, and symptoms of colitis in genetically modified mice.
- Examined the expression of small proline-rich proteins (SPRRs) and assessed the candidacidal activity of Sprr2a1 in vitro.
Main Results:
- Mice deficient in both IL-17RA and IL-22RA1 exhibited severe OPC, high fungal burdens in the esophagus and intestines, significant weight loss, and colitis.
- Dual cytokine receptor deficiency led to impaired expression of SPRRs.
- Sprr2a1 demonstrated direct killing activity against Candida in vitro, and mice lacking Sprr1-3a were susceptible to OPC.
Conclusions:
- Cooperative signaling of Type 17 cytokines (IL-17 and IL-22) is essential for effective oral mucosal defense against Candida fungal infections.
- Small proline-rich proteins (SPRRs) are identified as critical antimicrobial effectors in fungal immunity, particularly against OPC.
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