1. Academic Validation
  2. Caspase-8 drove apoptosis of BMECs to promote neutrophil infiltration and DE205B clearance in meningitis

Caspase-8 drove apoptosis of BMECs to promote neutrophil infiltration and DE205B clearance in meningitis

  • Microbiol Res. 2025 Sep:298:128223. doi: 10.1016/j.micres.2025.128223.
Xuhang Wang 1 Wanqiu Lin 1 Linlin Ye 1 Xinru Chen 1 Jianluan Ren 1 Feng Xue 2 Jianjun Dai 3 Fang Tang 4
Affiliations

Affiliations

  • 1 MOE Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Bacteriology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
  • 2 MOE Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Bacteriology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
  • 3 MOE Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Bacteriology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: daijianjun@njau.edu.cn.
  • 4 MOE Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Bacteriology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China; School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: tfalice@126.com.
Abstract

Avian pathogenic Escherichia coli (APEC), a significant virulence reservoir for human extraintestinal pathogenic E. coli (ExPEC), poses an escalating zoonotic risk through the food chain. Our previous study demonstrated that the poultry-derived strain DE205B shared high genetic similarity with the neonatal meningitis-associated E. coli (NMEC) strain RS218 and induced meningitis in a rat model. Here, we further demonstrated that DE205B crossed the blood-brain barrier (BBB) via a transcellular pathway without compromising barrier integrity. During this process, brain microvascular endothelial cells (BMECs) trigger limited RIPK1-independent Apoptosis. Mechanistically, Caspase-8 activation in BMECs drove the release of proinflammatory mediators, thereby promoting neutrophil recruitment into the cerebrospinal fluid (CSF). These neutrophils facilitated Bacterial clearance through the formation of neutrophil extracellular traps (NETs). In vivo pharmacological inhibition of Caspase-8 attenuated the ability of BMECs to recruit neutrophils, exacerbating meningitis progression. These findings suggested that limited Apoptosis of BMECs contributed positively to APEC clearance in the brain. Collectively, this study systematically elucidated mechanisms underlying DE205B-mediated BBB invasion and host immune responses, providing insights into its cross-species pathogenic potential and zoonotic implications.

Keywords

APEC; Apoptosis; Caspase-8; Meningitis; Zoonotic.

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