The Extracellular Matrix of Candida albicans Biofilms Impairs Formation of Neutrophil Extracellular Traps

PLoS Pathogens

Steven X. Wang¹  David J. Beebe¹  Anna Huttenlocher²  John F. Kernien³  Chad J. Johnson³  Jeniel E. Nett³  Jonathan Cabezas-Olcoz³  Hamayail Ansari⁴ 

[1] Department of Biomedical Engineering, University of Wisconsin, Madison, Wisconsin, United States of America;Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, United States of America;Department of Medicine, University of Wisconsin, Madison, Wisconsin, United States of America;Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, United States of America

关键词: Biofilms;    Neutrophils;    C;    ida albicans;    Extracellular matrix;    C;    ida;    Scanning electron microscopy;    Catheters;    Fluorescence imaging;   

DOI  :  10.1371/journal.ppat.1005884

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Neutrophils release extracellular traps (NETs) in response to planktonic C. albicans. These complexes composed of DNA, histones, and proteins inhibit Candida growth and dissemination. Considering the resilience of Candida biofilms to host defenses, we examined the neutrophil response to C. albicans during biofilm growth. In contrast to planktonic C. albicans, biofilms triggered negligible release of NETs. Time lapse imaging confirmed the impairment in NET release and revealed neutrophils adhering to hyphae and migrating on the biofilm. NET inhibition depended on an intact extracellular biofilm matrix as physical or genetic disruption of this component resulted in NET release. Biofilm inhibition of NETosis could not be overcome by protein kinase C activation via phorbol myristate acetate (PMA) and was associated with suppression of neutrophil reactive oxygen species (ROS) production. The degree of impaired NET release correlated with resistance to neutrophil attack. The clinical relevance of the role for extracellular matrix in diminishing NET production was corroborated in vivo using a rat catheter model. The C. albicans pmr1Δ/Δ, defective in production of matrix mannan, appeared to elicit a greater abundance of NETs by scanning electron microscopy imaging, which correlated with a decreased fungal burden. Together, these findings show that C. albicans biofilms impair neutrophil response through an inhibitory pathway induced by the extracellular matrix.

【 授权许可】

CC BY