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2016 ; 12
(9
): e1005884
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The Extracellular Matrix of Candida albicans Biofilms Impairs Formation of
Neutrophil Extracellular Traps
#MMPMID27622514
Johnson CJ
; Cabezas-Olcoz J
; Kernien JF
; Wang SX
; Beebe DJ
; Huttenlocher A
; Ansari H
; Nett JE
PLoS Pathog
2016[Sep]; 12
(9
): e1005884
PMID27622514
show ga
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 pmr1?/?, 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.