Pathogenesis of Vascular Infections unit, INSERM, Institut Pasteur, Paris, France.
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Nat Commun. 2021 Jul 27;12(1):4547. doi: 10.1038/s41467-021-24797-z.
The human pathogen Neisseria meningitidis can cause meningitis and fatal systemic disease. The bacteria colonize blood vessels and rapidly cause vascular damage, despite a neutrophil-rich inflammatory infiltrate. Here, we use a humanized mouse model to show that vascular colonization leads to the recruitment of neutrophils, which partially reduce bacterial burden and vascular damage. This partial effect is due to the ability of bacteria to colonize capillaries, venules and arterioles, as observed in human samples. In venules, potent neutrophil recruitment allows efficient bacterial phagocytosis. In contrast, in infected capillaries and arterioles, adhesion molecules such as E-Selectin are not expressed on the endothelium, and intravascular neutrophil recruitment is minimal. Our results indicate that the colonization of capillaries and arterioles by N. meningitidis creates an intravascular niche that precludes the action of neutrophils, resulting in immune escape and progression of the infection.
人类病原体脑膜炎奈瑟菌可引起脑膜炎和致命性全身疾病。尽管中性粒细胞丰富的炎症浸润,但细菌会迅速定植于血管并导致血管损伤。在这里,我们使用人源化小鼠模型表明,血管定植导致中性粒细胞的募集,这部分减轻了细菌负担和血管损伤。这种部分效应是由于细菌定植于毛细血管、小静脉和小动脉的能力所致,这在人类样本中得到了观察。在小静脉中,有效的中性粒细胞募集可促进细菌吞噬。相比之下,在受感染的毛细血管和小动脉中,内皮细胞上不表达粘附分子如 E-选择素,血管内中性粒细胞募集极少。我们的结果表明,脑膜炎奈瑟菌定植于毛细血管和小动脉,形成了一个血管内小生境,使中性粒细胞无法发挥作用,从而导致免疫逃逸和感染进展。