Tan Xi, Petri Björn, DeVinney Rebekah, Jenne Craig N, Chaconas George
Department of Biochemistry & Molecular Biology, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada.
Department of Microbiology, Immunology & Infectious Diseases, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada.
Mol Microbiol. 2021 Aug;116(2):498-515. doi: 10.1111/mmi.14728. Epub 2021 May 11.
Lyme disease is the most common tick-transmitted disease in the northern hemisphere and is caused by the spirochete Borrelia burgdorferi and related Borrelia species. The constellation of symptoms attributable to this malady results from vascular dissemination of B. burgdorferi throughout the body to invade various tissue types. However, little is known about the mechanism by which the spirochetes can breach the blood vessel wall to reach distant tissues. We have studied this process by direct observation of spirochetes in the microvasculature of living mice using multi-laser spinning-disk intravital microscopy. Our results show that in our experimental system, instead of phagocytizing B. burgdorferi, host neutrophils are involved in the production of specific cytokines that activate the endothelium and potentiate B. burgdorferi escape into the surrounding tissue. Spirochete escape is not induced by paracellular permeability and appears to occur via a transcellular pathway. Neutrophil repurposing to promote bacterial extravasation represents a new and innovative pathogenic strategy.
莱姆病是北半球最常见的蜱传播疾病，由螺旋体伯氏疏螺旋体及相关的疏螺旋体物种引起。这种疾病的一系列症状是由伯氏疏螺旋体在全身的血管扩散以侵入各种组织类型所致。然而，关于螺旋体能够突破血管壁到达远处组织的机制，人们知之甚少。我们通过使用多激光旋转盘活体显微镜直接观察活体小鼠微血管中的螺旋体来研究这一过程。我们的结果表明，在我们的实验系统中，宿主中性粒细胞并非吞噬伯氏疏螺旋体，而是参与特定细胞因子的产生，这些细胞因子激活内皮细胞并增强伯氏疏螺旋体向周围组织的逃逸。螺旋体的逃逸不是由细胞旁通透性诱导的，似乎是通过跨细胞途径发生的。中性粒细胞重新发挥作用以促进细菌外渗代表了一种新的创新致病策略。
