Environmental dimensionality controls the interaction of phagocytes with the pathogenic fungi Aspergillus fumigatus and Candida albicans

被引:85
作者
Behnsen, Judith
Narang, Priyanka
Hasenberg, Mike
Gunzer, Frank
Bilitewski, Ursula
Klippel, Nina
Rohde, Manfred
Brock, Matthias
Brakhage, Axel A.
Gunzer, Matthias [1 ]
机构
[1] Helmholtz Ctr Infect Res, Braunschweig, Germany
[2] Hans Knoll Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Mol & Appl Microbiol, Jena, Germany
[3] German Univ Cairo, Dept Phys, New Cairo City, Egypt
关键词
D O I
10.1371/journal.ppat.0030013
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页码:138 / 151
页数:14
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