Stage Specific Assessment of Candida albicans Phagocytosis by Macrophages Identifies Cell Wall Composition and Morphogenesis as Key Determinants
| Autor: | Collette Gillespie, Fiona M. Rudkin, Leanne E. Lewis, Neil A. R. Gow, Judith M. Bain, Lars P. Erwig, Christina Lowes |
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| Rok vydání: | 2012 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
Glycosylation Hypha Immune Cells Phagocytosis Immunology Morphogenesis Video microscopy Mycology Biology Microbiology Mice 03 medical and health sciences Cell Movement Cell Wall Virology Candida albicans Genetics Animals Macrophage lcsh:QH301-705.5 Molecular Biology 030304 developmental biology Mice Inbred BALB C 0303 health sciences Innate immune system 030306 microbiology fungi Candidiasis biology.organism_classification Immunity Innate Corpus albicans Cell biology Disease Models Animal lcsh:Biology (General) Macrophages Peritoneal Female Parasitology lcsh:RC581-607 Research Article |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 8, Iss 3, p e1002578 (2012) PLoS Pathogens; Vol 8 |
| ISSN: | 1553-7374 |
| Popis: | Candida albicans is a major life-threatening human fungal pathogen. Host defence against systemic Candida infection relies mainly on phagocytosis of fungal cells by cells of the innate immune system. In this study, we have employed video microscopy, coupled with sophisticated image analysis tools, to assess the contribution of distinct C. albicans cell wall components and yeast-hypha morphogenesis to specific stages of phagocytosis by macrophages. We show that macrophage migration towards C. albicans was dependent on the glycosylation status of the fungal cell wall, but not cell viability or morphogenic switching from yeast to hyphal forms. This was not a consequence of differences in maximal macrophage track velocity, but stems from a greater percentage of macrophages pursuing glycosylation deficient C. albicans during the first hour of the phagocytosis assay. The rate of engulfment of C. albicans attached to the macrophage surface was significantly delayed for glycosylation and yeast-locked morphogenetic mutant strains, but enhanced for non-viable cells. Hyphal cells were engulfed at a slower rate than yeast cells, especially those with hyphae in excess of 20 µm, but there was no correlation between hyphal length and the rate of engulfment below this threshold. We show that spatial orientation of the hypha and whether hyphal C. albicans attached to the macrophage via the yeast or hyphal end were also important determinants of the rate of engulfment. Breaking down the overall phagocytic process into its individual components revealed novel insights into what determines the speed and effectiveness of C. albicans phagocytosis by macrophages. Author Summary Host defence against systemic candidiasis relies mainly on the ingestion and elimination of fungal cells by cells of the innate immune system, especially neutrophils and macrophages. Here we have used live cell video microscopy coupled with sophisticated image analysis to generate a temporal and spatial analysis in unprecedented detail of the specific effects of C. albicans viability, cell wall composition, morphogenesis and spatial orientation on two distinct stages (macrophage migration and engulfment of bound C. albicans) of the phagocytosis process. The novel methods employed here to study phagocytosis of C. albicans could be applied to study other pathogens and uptake of dying host cells. Thus, our studies have direct implications for a much broader community and provide a blueprint for future studies with other phagocytes/microorganisms that would significantly enhance our understanding of the mechanisms that govern effective phagocytosis and ultimately the innate immune response to infection. |
| Databáze: | OpenAIRE |
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