2. Academic Validation
  3. In toto imaging shows intravascular proliferation promotes transmigration of daughter cells during brain invasion of Cryptococcus neoformans

In toto imaging shows intravascular proliferation promotes transmigration of daughter cells during brain invasion of Cryptococcus neoformans

  • Cell Rep. 2025 Dec 23;44(12):116658. doi: 10.1016/j.celrep.2025.116658.
Ge Wang 1,  Chenxu Feng 1,  Ziyi Ma 1,  Lu Zhao 2,  Mohammed Yosri 3,  Yixuan Wang 1,  Xiang Gao 1,  Weiwei Zhu 1,  Hongmei Li 4,  Haihan Song 5,  Jianhua Xia 5,  Mei Meng 6,  Hongzhong Lu 7,  Lisheng Zhang 2,  Zongyan Chen 8,  Donglei Sun 9
Affiliations

Affiliations

  • 1 Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 2 Key Laboratory of Animal Biosafety Risk Prevention and Control of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China.
  • 3 The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo 11651, Egypt.
  • 4 Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
  • 5 Department of Anesthesiology, Shanghai Pudong New Area People's Hospital, Shanghai 201299, China.
  • 6 Department of Critical Care Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
  • 7 State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 8 Key Laboratory of Animal Biosafety Risk Prevention and Control of Ministry of Agriculture and Rural Affairs, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China. Electronic address: [email protected].
  • 9 Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; Shanghai Key Laboratory for Antibody-Drug Conjugates with Innovative Target, Shanghai 200240, China. Electronic address: [email protected].
PMID: 41351837 DOI: 10.1016/j.celrep.2025.116658
Abstract

Cryptococcus neoformans causes lethal meningoencephalitis. Although the mechanism of its blood-brain barrier (BBB) transmigration has been intensively studied, the predominant route remains unclear. We developed fTRACE, a whole-organ imaging workflow enabling in toto visualization of individual Fungal cells in vivo, and found that C. neoformans can proliferate intravascularly before BBB transmigration. Importantly, daughter cells, not mother cells, predominantly transmigrate across the BBB. Intravascular proliferation depends on de novo purine biosynthesis. We created a non-proliferative fluorescent mutant to trace Fungal fate in the brain and found that the majority of non-proliferative C. neoformans remained intravascular after prolonged brain Infection, while the remainder induced local capillary pruning. Angiophagy occurred with low frequency. C. neoformans can be washed out from the brain vasculature, which is expedited by VEGFR-2 inhibition. This study elucidates a major brain invasion route of C. neoformans and provides an approach for studying host-pathogen interactions using in toto imaging.

Keywords

CP: microbiology; Cryptococcus neoformans; blood-brain barrier; imaging; intravascular proliferation; purine biosynthesis.

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