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Published on: April 19, 2017
A novel pseudopodial component of the dendritic cell anti-fungal response: the fungipod
Aaron K Neumann1, Ken Jacobson
1Department of Cell & Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Abstract:
Fungal pathologies are seen in immunocompromised and healthy humans. C-type lectins expressed on immature dendritic cells (DC) recognize fungi. We report a novel dorsal pseudopodial protrusion, the "fungipod", formed by DC after contact with yeast cell walls. These structures have a convoluted cell-proximal end and a smooth distal end. They persist for hours, exhibit noticeable growth and total 13.7+/-5.6 microm long and 1.8+/-0.67 microm wide at the contact. Fungipods contain clathrin and an actin core surrounded by a sheath of cortactin. The actin cytoskeleton, but not microtubules, is required for fungipod integrity and growth. An apparent rearward flow (225+/-55 nm/second) exists from the zymosan contact site into the distal fungipod. The phagocytic receptor Dectin-1 is not required for fungipod formation, but CD206 (Mannose Receptor) is the generative receptor for these protrusions. The human pathogen Candida parapsilosis induces DC fungipod formation strongly, but the response is species specific since the related fungal pathogens Candida tropicalis and Candida albicans induce very few and no fungipods, respectively. Our findings show that fungipods are dynamic actin-driven cellular structures involved in fungal recognition by DC. They may promote yeast particle phagocytosis by DC and are a specific response to large (i.e., 5 microm) particulate ligands. Our work also highlights the importance of this novel protrusive structure to innate immune recognition of medically significant Candida yeasts in a species specific fashion.
Insights
Dendritic cells (DCs) form novel "fungipods" to recognize fungal cell walls. These actin-driven structures, generated by the Mannose Receptor (CD206), are crucial for innate immune responses to specific Candida species.
Area of Science:
- Immunology
- Cell Biology
- Mycology
Background:
- Fungal infections affect both healthy and immunocompromised individuals.
- Immature dendritic cells (DCs) use C-type lectins to recognize fungi.
- Understanding fungal recognition mechanisms is vital for innate immunity.
Purpose of the Study:
- To identify and characterize novel cellular structures involved in fungal recognition by DCs.
- To elucidate the molecular mechanisms and receptors responsible for fungal recognition.
- To investigate the species-specific responses of DCs to different Candida yeasts.
Main Methods:
- Microscopy to visualize and measure novel cellular protrusions (fungipods).
- Immunofluorescence staining to identify cellular components (clathrin, actin, cortactin) within fungipods.
- Genetic or pharmacological inhibition to assess the role of cytoskeleton (actin, microtubules) in fungipod formation and stability.
- Receptor blocking or knockout studies to determine the role of Dectin-1 and CD206 in fungipod induction.
- Exposure of DCs to different Candida species (C. parapsilosis, C. tropicalis, C. albicans) to assess species-specific responses.
Main Results:
- A novel dorsal pseudopodial protrusion, termed 'fungipod', is formed by DCs upon contact with yeast cell walls.
- Fungipods are dynamic, actin-driven structures (13.7+/-5.6 µm long) containing clathrin and cortactin, requiring an intact actin cytoskeleton for integrity and growth.
- Mannose Receptor (CD206), not Dectin-1, is the generative receptor for fungipod formation.
- Candida parapsilosis strongly induces fungipod formation, while C. tropicalis and C. albicans induce significantly fewer or no fungipods, indicating species-specific recognition.
- An apparent rearward flow of material from the contact site into the fungipod was observed.
Conclusions:
- Fungipods are novel, dynamic, actin-driven cellular structures critical for fungal recognition by dendritic cells.
- CD206 (Mannose Receptor) is the key receptor mediating fungipod formation in response to fungal particles.
- The formation of fungipods is a species-specific innate immune response, particularly important for recognizing medically significant Candida yeasts.
- These structures may play a role in enhancing yeast particle phagocytosis by DCs.
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