Trypanosoma brucei is responsible for lethal diseases in humans and cattle in Sub-Saharan Africa. These extracellular parasites extravasate from the blood circulation into several tissues. The importance of the vasculature in tissue tropism is poorly understood. Using intravital imaging and bioluminescence, we observe that gonadal white adipose tissue and pancreas are the two main parasite reservoirs. We show that reservoir establishment happens before vascular permeability is compromised, suggesting that extravasation is an active mechanism. Blocking endothelial surface adhesion molecules (E-selectin, P-selectins, or ICAM2) significantly reduces extravascular parasite density in all organs and delays host lethality. Remarkably, blocking CD36 has a specific effect on adipose tissue tropism that is sufficient to delay lethality, suggesting that establishment of the adipose tissue reservoir is necessary for parasite virulence. This work demonstrates the importance of the vasculature in a T. brucei infection and identifies organ-specific adhesion molecules as key players for tissue tropism.

布氏锥虫负责撒哈拉以南非洲人类和牛的致命疾病。这些细胞外寄生虫从血液循环中渗出到几个组织中。脉管系统在组织趋向性中的重要性知之甚少。使用活体成像和生物发光，我们观察到性腺白色脂肪组织和胰腺是两个主要的寄生虫储存库。我们表明储层的建立发生在血管渗透性受损之前，这表明外渗是一种主动机制。阻断内皮表面粘附分子（E-选择素、P-选择素或 ICAM2）可显着降低所有器官中的血管外寄生虫密度并延迟宿主致死率。值得注意的是，阻断 CD36 对脂肪组织嗜性具有特定作用，足以延迟致死率，表明脂肪组织储库的建立对于寄生虫的毒力是必要的。这项工作证明了脉管系统在T. brucei感染并确定器官特异性粘附分子是组织趋向性的关键参与者。