Environmental Dimensionality Controls the Interaction of Phagocytes with the Pathogenic Fungi Aspergillus fumigatus and Candida albicans

PLoS Pathogens

Axel A Brakhage¹  Judith Behnsen¹  Matthias Brock¹  Frank Gunzer²  Manfred Rohde³  Ursula Bilitewski³  Nina Klippel³  Matthias Gunzer³  Priyanka Narang³  Mike Hasenberg³ 

[1] Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany;Department of Physics, The German University of Cairo, New Cairo City, Egypt;Helmholtz Centre for Infection Research, Braunschweig, Germany

关键词: Aspergillus fumigatus;    Phagocytosis;    C;    ida albicans;    Phagocytes;    Collagens;    Fungal pathogens;    Macrophages;    Yeast;   

DOI  :  10.1371/journal.ppat.0030013

学科分类：生物科学（综合）

来源: Public Library of Science

【 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.

【 授权许可】

CC BY