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Th17 Inflammation Model of Oropharyngeal Candidiasis in Immunodeficient Mice
Published on: February 18, 2015
Differential IL-17 production and mannan recognition contribute to fungal pathogenicity and commensalism
Lisa Rizzetto1, Mirela Kuka, Carlotta De Filippo
1Department of Preclinic and Clinic Pharmacology, University of Firenze, Firenze, Italy.
Abstract:
In this study, we present evidence of differential Th17 responses in human monocyte-derived dendritic cells exposed to the pathogenic Candida albicans or the nonpathogenic Saccharomyces cerevisiae. We use different forms of the microorganisms, cells, hyphae, and spores, as a toolbox to dissect the role of surface mannan in the fungal immune response. In contrast to the S. cerevisiae yeast cell-induced Th1 response, dendritic cells stimulated with spores or C. albicans hyphae induce cellular responses shifted toward Th17 differentiation. The differential recognition of specific mannan structures is the master regulator of the discrimination between harmful and harmless fungi. The switch between spores and yeast is crucial for the commensalism of S. cerevisiae and depends on the use of a different receptor repertoire. Understanding the role of cell wall recognition during infection might lead to understanding the boundaries between safety and pathogenicity.
Insights
Pathogenic Candida albicans spores and hyphae trigger distinct Th17 immune responses in dendritic cells, unlike nonpathogenic Saccharomyces cerevisiae yeast. Mannan structure recognition differentiates harmful from harmless fungi, impacting immune responses.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Fungal infections pose significant health challenges.
- Differentiating between pathogenic and commensal fungi is crucial for immune homeostasis.
- Dendritic cells play a key role in initiating adaptive immune responses to fungi.
Purpose of the Study:
- To investigate differential immune responses to pathogenic Candida albicans and nonpathogenic Saccharomyces cerevisiae.
- To dissect the role of fungal surface mannan in immune recognition.
- To understand how fungal morphology influences T helper cell differentiation.
Main Methods:
- Human monocyte-derived dendritic cells were exposed to different forms of C. albicans and S. cerevisiae (yeast, hyphae, spores).
- Flow cytometry and cytokine analysis were used to assess T helper 17 (Th17) and T helper 1 (Th1) cell responses.
- Surface mannan structures were analyzed for their role in differential recognition.
Main Results:
- Dendritic cells stimulated with C. albicans hyphae or S. cerevisiae spores induced a shift towards Th17 differentiation.
- S. cerevisiae yeast cells induced a Th1 immune response.
- Differential recognition of specific mannan structures regulated the discrimination between pathogenic and nonpathogenic fungi.
Conclusions:
- Fungal cell wall mannan structures are critical regulators in distinguishing harmful from harmless fungi.
- The switch between yeast and spore forms in S. cerevisiae is essential for commensalism, mediated by distinct receptor usage.
- Understanding fungal cell wall recognition is key to defining the balance between safety and pathogenicity in fungal infections.
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