CNRS UPR 3572, IBMC, University of Strasbourg, Strasbourg, France.
Signalling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
EMBO Rep. 2023 Apr 5;24(4):e55971. doi: 10.15252/embr.202255971. Epub 2023 Mar 1.
Pseudomonas aeruginosa is a Gram-negative bacterium causing morbidity and mortality in immuno-compromised humans. It produces a lectin, LecB, that is considered a major virulence factor, however, its impact on the immune system remains incompletely understood. Here we show that LecB binds to endothelial cells in human skin and mice and disrupts the transendothelial passage of leukocytes in vitro. It impairs the migration of dendritic cells into the paracortex of lymph nodes leading to a reduced antigen-specific T cell response. Under the effect of the lectin, endothelial cells undergo profound cellular changes resulting in endocytosis and degradation of the junctional protein VE-cadherin, formation of an actin rim, and arrested cell motility. This likely negatively impacts the capacity of endothelial cells to respond to extracellular stimuli and to generate the intercellular gaps for allowing leukocyte diapedesis. A LecB inhibitor can restore dendritic cell migration and T cell activation, underlining the importance of LecB antagonism to reactivate the immune response against P. aeruginosa infection.
铜绿假单胞菌是一种革兰氏阴性细菌，可导致免疫功能低下的人群发病和死亡。它产生一种凝集素 LecB，被认为是主要的毒力因子，但它对免疫系统的影响仍不完全清楚。在这里，我们表明 LecB 与人皮肤和小鼠的内皮细胞结合，并破坏体外白细胞的跨内皮迁移。它会损害树突状细胞迁移到淋巴结的副皮质，导致抗原特异性 T 细胞反应减少。在凝集素的作用下，内皮细胞发生深刻的细胞变化，导致细胞连接蛋白 VE-钙黏蛋白的内吞和降解、肌动蛋白环的形成以及细胞运动的停滞。这可能会对内皮细胞对外界刺激做出反应并产生允许白细胞穿出的细胞间间隙的能力产生负面影响。LecB 抑制剂可以恢复树突状细胞的迁移和 T 细胞的激活，这强调了拮抗 LecB 以重新激活针对铜绿假单胞菌感染的免疫反应的重要性。
