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Published on: December 19, 2014
Phagocytic podosomes enable efficient uptake of Candida auris by primary human macrophages
Konstantin Sopelniak1, Rawan Batlouni1, Qifan Sun1
1Institut für medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
Abstract:
The yeast Candida auris is an emerging pathogen. Understanding the molecular mechanisms of its uptake and processing by immune cells is thus critical for counteracting the spread of respective infections. We show that the phagocytosis of C. auris cells by primary human macrophages involves the formation of dot-like F-actin-rich structures at C. auris-containing phagosomes that we characterize as phagocytic podosomes. We analyze the composition, architecture, and dynamics of these structures, showing that they constitute a specific adaptation of the phagocytic actin network. The disruption of phagocytic podosomes is associated with reduced internalization of C. auris and delayed phagosomal maturation. Our data provide detailed insights into cytoskeletal rearrangements upon internalization of Candida by immune cells while also demonstrating that the actin network within phagocytic cups is not necessarily uniform and continuous. At the same time, we identify C. auris as a pathophysiologically relevant target whose internalization involves the formation of phagocytic podosomes.
Insights
The study reveals that immune cells form specialized actin structures called phagocytic podosomes to engulf the emerging pathogen Candida auris. Disrupting these structures impairs fungal uptake and processing, offering new insights into host-pathogen interactions.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Candida auris is an emerging fungal pathogen causing significant public health concerns.
- Understanding how immune cells interact with and eliminate C. auris is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the uptake and processing of Candida auris by human macrophages.
- To characterize the role of cytoskeletal rearrangements, specifically F-actin structures, during C. auris phagocytosis.
Main Methods:
- Utilized primary human macrophages to study phagocytosis of C. auris.
- Analyzed the composition, architecture, and dynamics of F-actin-rich structures formed at phagosomes.
- Investigated the impact of disrupting these structures on fungal internalization and phagosomal maturation.
Main Results:
- Identified dot-like F-actin structures, termed phagocytic podosomes, at C. auris-containing phagosomes.
- Demonstrated that phagocytic podosomes are a specific adaptation of the phagocytic actin network.
- Showed that disruption of phagocytic podosomes leads to reduced C. auris internalization and delayed phagosomal maturation.
Conclusions:
- Phagocytic podosomes play a critical role in the efficient uptake and processing of Candida auris by macrophages.
- Cytoskeletal rearrangements during fungal internalization are complex and can involve non-uniform actin networks.
- C. auris represents a relevant target for immune cell internalization mechanisms involving phagocytic podosomes.
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