title: Environmental dimensionality controls the interaction of phagocytes with the pathogenic fungi Aspergillus fumigatus and Candida albicans.
abstract: The fungal pathogens Aspergillus fumigatus and Candida albicans are major health threats for immune-compromised patients. Normally, macrophages and neutrophil granulocytes phagocytose inhaled Aspergillus conidia in the two-dimensional (2-D) environment of the alveolar lumen or Candida growing in tissue microabscesses, which are composed of a three-dimensional (3-D) extracellular matrix. However, neither the cellular dynamics, the per-cell efficiency, the outcome of this interaction, nor the environmental impact on this process are known. Live imaging shows that the interaction of phagocytes with Aspergillus or Candida in 2-D liquid cultures or 3-D collagen environments is a dynamic process that includes phagocytosis, dragging, or the mere touching of fungal elements. Neutrophils and alveolar macrophages efficiently phagocytosed or dragged Aspergillus conidia in 2-D, while in 3-D their function was severely impaired. The reverse was found for phagocytosis of Candida. The phagocytosis rate was very low in 2-D, while in 3-D most neutrophils internalized multiple yeasts. In competitive assays, neutrophils primarily incorporated Aspergillus conidia in 2-D and Candida yeasts in 3-D despite frequent touching of the other pathogen. Thus, phagocytes show activity best in the environment where a pathogen is naturally encountered. This could explain why "delocalized" Aspergillus infections such as hematogeneous spread are almost uncontrollable diseases, even in immunocompetent individuals.
authors.affiliation: Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Behnsen
authors.forename: Priyanka
authors.initials: P
authors.lastname: Narang
authors.forename: Mike
authors.initials: M
authors.lastname: Hasenberg
authors.forename: Frank
authors.initials: F
authors.lastname: Gunzer
authors.forename: Ursula
authors.initials: U
authors.lastname: Bilitewski
authors.forename: Nina
authors.initials: N
authors.lastname: Klippel
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Matthias
authors.initials: M
authors.lastname: Brock
authors.forename: Axel A
authors.initials: AA
authors.lastname: Brakhage
authors.forename: Matthias
authors.initials: M
authors.lastname: Gunzer
mesh_terms: D000818:Animals; D001232:Aspergillus fumigatus / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D004777:Environment; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D010586:Phagocytes / Q000276:immunology*; D010587:Phagocytosis; D011401:Promoter Regions, Genetic
chemical_list: D008164:Luminescent Proteins; C413663:fluorescent protein 583