Human Conventional and Plasmacytoid Dendritic Cells Differ in Their Ability to Respond to Saccharomyces cerevisiae

Area of Science:

• Immunology
• Mycology
• Cell Biology

Background:

• Saccharomyces cerevisiae is a common yeast, acting as both a commensal and an opportunistic pathogen.
• Previous studies focused on Saccharomyces cerevisiae interactions with monocyte-derived dendritic cells and peripheral blood mononuclear cells.
• The immune response of blood-circulating dendritic cells (DCs) to Saccharomyces cerevisiae remained largely uninvestigated.

Purpose of the Study:

• To investigate the response of human conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs) to Saccharomyces cerevisiae.
• To elucidate the distinct sensing mechanisms and cytokine production profiles of DC subsets upon yeast encounter.

Main Methods:

• Isolation and stimulation of human cDCs and pDCs with Saccharomyces cerevisiae.
• Analysis of cytokine production (e.g., IL-6, IFN-α) and cell surface marker expression.
• Assessment of T helper cell polarization induced by stimulated DC subsets.

Main Results:

• Both cDCs and pDCs recognize Saccharomyces cerevisiae.
• cDCs produce IL-6, express activation markers, and promote T helper 17 cell polarization.
• pDCs uniquely sense fungal nucleic acids, generating P1-pDCs that produce IFN-α and induce IL-10-producing T helper cells.

Conclusions:

• Human conventional DCs respond to Saccharomyces cerevisiae similarly to monocyte-derived DCs.
• Plasmacytoid DCs play a novel role in sensing fungal nucleic acids from Saccharomyces cerevisiae, producing IFN-α and influencing T helper cell responses.
• These findings suggest a significant role for pDCs in regulating host microbiota-immune system balance and anti-fungal immunity.