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

  • Microbial Genetics, Genomics and Molecular Biology
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Abstract

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 non-endemic 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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Authors and Affiliations

  1. Department 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

    Ding Li, Changsen Bai, Qing Zhang & Zheng Li

  2. Denali Medpharma Co., Ltd, Chongqing, 400000, P. R. China

    Di Shao

  3. Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Sciences, Tianjin Normal University, Tianjin, 300387, P. R. China

    Xichuan Li

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  1. Ding Li
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  2. Changsen Bai
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  3. Qing Zhang
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  4. Zheng Li
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  5. Di Shao
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  6. Xichuan Li
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Correspondence to Ding Li, Di Shao or Xichuan Li.

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Li, D., Bai, C., Zhang, Q. et al. β-1,3-Glucan/CR3/SYK pathway-dependent LC3B-II accumulation enhanced the fungicidal activity in human neutrophils. J Microbiol. 57, 263–270 (2019). https://doi.org/10.1007/s12275-019-8298-1

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