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β-1,3-Glucan/CR3/SYK pathway-dependent LC3B-II accumulation enhanced the fungicidal activity in human neutrophils

Ding Li1, Changsen Bai2, Qing Zhang2

  • 1Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, P. R. China. lidingly@126.com.

Journal of Microbiology (Seoul, Korea)
|February 6, 2019
PubMed

Insights

Endemic Candida strains cause more severe invasive candidiasis. Neutrophils kill endemic strains less effectively due to reduced β-1,3-glucan exposure, impacting infection control strategies.

Area of Science:

  • Mycology
  • Immunology
  • Infectious Diseases

Background:

  • Molecular genotyping reveals persistent endemic Candida strains causing nosocomial invasive candidiasis.
  • Previous research identified endemic strains in a Chinese cancer center.

Purpose of the Study:

  • Investigate the higher morbidity associated with endemic Candida albicans strains.
  • Explain the mechanisms behind differential neutrophil killing of endemic versus non-endemic strains.

Main Methods:

  • In vivo experiments using mice to assess survival and fungal burden.
  • In vitro neutrophil killing assays.
  • Immunofluorescence assays to analyze cell wall β-1,3-glucan exposure.
  • Experiments involving blocking the β-glucan receptor (CR3) or inhibiting the SYK pathway in neutrophils.

Main Results:

  • Mice infected with endemic strains had shorter survival and higher kidney fungal burdens.
  • Neutrophils exhibited significantly lower killing percentages against endemic strains.
  • Endemic strains showed less β-1,3-glucan exposure on their cell walls compared to non-endemic strains.
  • Blocking CR3 or inhibiting SYK decreased neutrophil killing of C. albicans and LC3B-II/I ratio.

Conclusions:

  • Neutrophil killing of Candida albicans is regulated by β-1,3-glucan via the CR3/SYK pathway, dependent on LC3B-II accumulation.
  • This mechanism explains variable neutrophil efficacy against different Candida strains.
  • Findings offer insights for improving invasive candidiasis infection control and therapies.
Keywords:
Candida albicansLC3Bimmune evasionneutrophilsβ-1,3-glucan

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