- β-1,3-Glucan/CR3/SYK pathway-dependent LC3B-II accumulation enhanced the fungicidal activity in human neutrophils
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Ding Li , Changsen Bai , Qing Zhang , Zheng Li , Di Shao , Xichuan Li
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J. Microbiol. 2019;57(4):263-270. Published online February 5, 2019
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DOI: https://doi.org/10.1007/s12275-019-8298-1
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 Abstract
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Since molecular genotyping has been established for the
Candida species, studies have found that a single Candida
strain (endemic strain) can persist over a long period of time
and results in the spread of nosocomial invasive candidiasis
without general characteristics of horizontal transmissions.
Our previous study also found the existence of endemic
strains in a cancer center in Tianjin, China. In the current
study, we performed further investigation on endemic and
non-endemic Candida albicans strains, with the aim of explaining
the higher morbidity of endemic strains. In an in
vivo experiment, mice infected with endemic strains showed
significantly shorter survival time and higher kidney fungal
burdens compared to mice infected with non-endemic strains.
In an in vitro experiment, the killing percentage of neutrophils
to endemic strains was significantly lower than that to
non-endemic strains, which is positively linked to the ratio
of LC3B-II/I in neutrophils. An immunofluorescence assay
showed more β-1,3-glucan exposure on the cell walls of nonendemic
strains compared to endemic strains. After blocking
the β-glucan receptor (CR3) or inhibiting downstream
kinase (SYK) in neutrophils, the killing percent to C. albicans
(regardless of endemic and non-endemic strains) and the ratio
of LC3B-II/I of neutrophils were significantly decreased.
These data suggested that the killing capability of neutrophils
to C. albicans was monitored by β-1,3-glucan via CR3/SYK
pathway-dependent LC3B-II accumulation and provided
an explanation for the variable killing capability of neutrophils
to different strains of C. albicans, which would be beneficial
in improving infection control and therapeutic strategies
for invasive candidiasis.
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