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Live-cell Video Microscopy of Fungal Pathogen Phagocytosis
Published on: January 9, 2013
Candida albicans Targets a Lipid Raft/Dectin-1 Platform to Enter Human Monocytes and Induce Antigen Specific T Cell
Valeria de Turris1,2, Raffaela Teloni3, Paola Chiani3
1Center for Life Nanoscience, Istituto Italiano di Tecnologia, 00161, Rome, Italy.
Abstract:
Several pathogens have been described to enter host cells via cholesterol-enriched membrane lipid raft microdomains. We found that disruption of lipid rafts by the cholesterol-extracting agent methyl-β-cyclodextrin or by the cholesterol-binding antifungal drug Amphotericin B strongly impairs the uptake of the fungal pathogen Candida albicans by human monocytes, suggesting a role of raft microdomains in the phagocytosis of the fungus. Time lapse confocal imaging indicated that Dectin-1, the C-type lectin receptor that recognizes Candida albicans cell wall-associated β-glucan, is recruited to lipid rafts upon Candida albicans uptake by monocytes, supporting the notion that lipid rafts act as an entry platform. Interestingly disruption of lipid raft integrity and interference with fungus uptake do not alter cytokine production by monocytes in response to Candida albicans but drastically dampen fungus specific T cell response. In conclusion, these data suggest that monocyte lipid rafts play a crucial role in the innate and adaptive immune responses to Candida albicans in humans and highlight a new and unexpected immunomodulatory function of the antifungal drug Amphotericin B.
Insights
Disrupting lipid rafts impairs Candida albicans uptake by monocytes. This suggests lipid rafts are crucial entry platforms for the fungus, impacting both innate and adaptive immune responses.
Area of Science:
- Immunology
- Cell Biology
- Mycology
Background:
- Pathogen entry into host cells often involves cholesterol-enriched membrane lipid raft microdomains.
- Lipid rafts are specialized membrane domains implicated in various cellular processes, including immune cell signaling and pathogen interactions.
Purpose of the Study:
- To investigate the role of lipid rafts in the uptake of the fungal pathogen Candida albicans by human monocytes.
- To determine the impact of lipid raft disruption on immune responses to Candida albicans.
Main Methods:
- Disruption of lipid rafts using methyl-β-cyclodextrin and Amphotericin B.
- Time-lapse confocal imaging to track Dectin-1 recruitment during Candida albicans uptake.
- Assessment of cytokine production and T cell responses following Candida albicans exposure.
Main Results:
- Disruption of lipid rafts significantly impaired Candida albicans uptake by human monocytes.
- Dectin-1, a key receptor for Candida albicans, was recruited to lipid rafts during fungal uptake.
- While cytokine production by monocytes was unaffected, T cell responses to Candida albicans were dampened upon lipid raft disruption.
Conclusions:
- Monocyte lipid rafts are critical for the phagocytosis of Candida albicans, acting as entry platforms.
- Lipid rafts play a significant role in both innate and adaptive immune responses to Candida albicans.
- The antifungal drug Amphotericin B exhibits an immunomodulatory function by affecting lipid raft integrity and subsequent immune responses.
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