Febrile temperature enhances Plasmodium falciparum and neutrophil adhesion by disrupting the endothelial glycocalyx
Introini, V.; Long, R.; Oyerinde, O. R.; Gestal-Mato, M.; Sender, S. S.; Rizo Alvarez, I. d. J.; Hartmann, L.; Stein, F.; Hwang, G. M.; Gutierrez, B. L.; Seydel, K. B.; Birbeck, G.; Bernabeu, M. · microbiology · 2026-09-07 · 原文
DOI：10.1101/2025.09.07.674757作者：13 位
Fever, a universal host defense response in infection and inflammation, paradoxically contributes to neurological complications in malaria. Febrile temperatures are known to enhance parasite virulence protein expression, but direct effects on the human endothelium remain unknown. We found that a 1-hour exposure to 40 {degrees}C, representative of fever in children with cerebral malaria, increased adhesion of Plasmodium falciparum-infected red blood cells and neutrophils to 3D brain microvascular models displaying a wide wall shear stress gradient. Mechanistically, this brief hyperthermia triggered rapid endothelial glycocalyx shedding, exposing endothelial receptors for binding. This response was more pronounced in brain than in pulmonary microvessels, revealing a greater vulnerability of the cerebral vasculature to fever. Pharmacological inhibition of matrix metalloproteinase activity preserved glycocalyx integrity and abolished the temperature-induced increase in adhesion. These findings identify fever as a host-specific amplifier of malaria-associated microvascular pathology, highlighting the importance of antipyretic strategies to mitigate disease severity.
讲义
讲义·推断 依据「原文」自动生成的结构化摘要（推断），非原文表述；以原文为准。
1. 人话版
Fever, a universal host defense response in infection and inflammation, paradoxically contributes to neurological complications in malaria.
Febrile temperatures are known to enhance parasite virulence protein expression, but direct effects on the human endothelium remain unknown.
2. 领域脉络
本文类目：microbiology，属于其所在研究脉络的最新进展。
3. 机制拆解
Mechanistically, this brief hyperthermia triggered rapid endothelial glycocalyx shedding, exposing endothelial receptors for binding.
This response was more pronounced in brain than in pulmonary microvessels, revealing a greater vulnerability of the cerebral vasculature to fever.
4. 证据与数字
We found that a 1-hour exposure to 40 {degrees}C, representative of fever in children with cerebral malaria, increased adhesion of Plasmodium falciparum-infected red blood cells and neutrophils to 3D brain microvascular models displaying a wide wall shear stress gradient.
5. 反例与边界
摘要未声明局限与反例——这是需要警惕的信号，精读时先问边界。
6. 跨领域连接与意外收获
思考本文机制能否迁移到你正在跟进的问题。
7. 可复用方法
把本文机制与你手头项目对照，找一个两周内能验证的最小实验。
8. 术语表
精读时把不熟的术语记入此处，作为下次回忆的锚点。