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Updated: Jul 5, 2025
Th17 Inflammation Model of Oropharyngeal Candidiasis in Immunodeficient Mice
Published on: February 18, 2015
Immunity to pathogenic mucosal C. albicans infections mediated by oral megakaryocytes activated by IL-17 and
Dylan Launder1, John T Dillon1, Leah M Wuescher2
1Department of Biological Sciences, University of Toledo, Toledo, Ohio, United States.
Abstract:
The fungus Candida albicans can cause mucosal infections including oropharyngeal candidiasis (OPC) in immunocompromised patients. In humans, an increased risk of fungal infections correlates with thrombocytopenia. However, our understanding of platelets and megakaryocytes (Mks) in mucosal fungal infections is almost entirely unknown. When megakaryocyte- and platelet-depleted mice were infected with OPC, the tongue showed higher fungal burden, due to decreased neutrophil accumulation. Protection depended on a distinct population of oral-resident Mks. Interleukin-17, important in antifungal immunity, was required since mice lacking the IL-17 receptor had decreased circulating platelets and their oral Mks did not expand during OPC. The secretion of the peptide toxin candidalysin activated human Mks to release platelets with antifungal capacity. Infection with a candidalysin-deficient strain resulted in decreased expansion of tongue Mks during OPC. This is the first time that a distinct megakaryocyte population was identified in the oral mucosa which is critical for immunity against fungal infection.
Insights
Platelets and megakaryocytes (Mks) are crucial for fighting fungal infections like oropharyngeal candidiasis (OPC). Oral Mks and platelets protect against Candida albicans by enhancing neutrophil accumulation.
Area of Science:
- Immunology
- Mycology
- Hematology
Background:
- Candida albicans causes mucosal infections, particularly oropharyngeal candidiasis (OPC), in immunocompromised individuals.
- Thrombocytopenia correlates with increased fungal infection risk, yet the roles of platelets and megakaryocytes (Mks) in mucosal fungal infections remain largely unexplored.
Purpose of the Study:
- To investigate the role of megakaryocytes (Mks) and platelets in mucosal immunity against Candida albicans.
- To elucidate the mechanisms by which Mks and platelets contribute to host defense during oropharyngeal candidiasis (OPC).
Main Methods:
- Utilized megakaryocyte- and platelet-depleted mouse models for OPC infection.
- Assessed fungal burden, neutrophil accumulation, and Mks populations in oral tissues.
- Investigated the role of Interleukin-17 (IL-17) signaling and the candidalysin toxin in Mks and platelet function.
Main Results:
- Megakaryocyte- and platelet-depleted mice exhibited increased fungal burden and reduced neutrophil accumulation in the tongue during OPC.
- A distinct population of oral-resident Mks was identified as critical for protection.
- IL-17 signaling was essential for maintaining circulating platelet counts and oral Mks expansion during OPC.
- Candidalysin activated human Mks to release antifungal platelets, and its absence impaired Mks expansion during infection.
Conclusions:
- Oral-resident megakaryocytes (Mks) and platelets play a vital role in mucosal antifungal immunity.
- The IL-17 pathway and candidalysin toxin are important regulators of Mks and platelet function in combating Candida albicans infections.
- This study identifies a novel role for oral Mks in host defense against fungal pathogens.
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