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.

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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