Xaplanteri Panagiota, Lagoumintzis George, Dimitracopoulos George, Paliogianni Fotini
Department of Microbiology, School of Medicine, University of Patras, Patras, Greece.
Eur J Immunol. 2009 Mar;39(3):730-40. doi: 10.1002/eji.200838872.
The immune response to pathogen is regulated by a combination of specific PRR, which are involved in pathogen recognition. Pseudomonas aeruginosa, a bacterium that causes life-threatening disease in immuno-compromised host, is recognized by distinct members of the TLR family. We have previously shown that viable P. aeruginosa bacteria are recognized by human monocytes mainly through TLR2. Using ligand-specific blocking antibodies, we herein show that the mannose receptor (MR), a phagocytic receptor for unopsonized P. aeruginosa bacteria, contributes equally to TLR2 in proinflammatory cytokine production by human monocytes in response to P. aeruginosa infection. Synergy of both receptors totally controls the immune response. Viable P. aeruginosa bacteria activate NF-kappaB and MAPK pathways and enhance TLR2-mediated signaling in MR-transfected human embryonic kidney 293 cells. Moreover, MR follows the same kinetics and colocalizes with TLR2 in the endosome during in vivo infection of human macrophages with P. aeruginosa. The studies provide the first demonstration of a significant role for MR, synergistic with TLR2, in activating a proinflammatory response to P. aeruginosa infection.
对病原体的免疫反应由参与病原体识别的特定模式识别受体（PRR）共同调节。铜绿假单胞菌是一种能在免疫功能低下的宿主中引发危及生命疾病的细菌，可被Toll样受体（TLR）家族的不同成员识别。我们之前已经表明，活的铜绿假单胞菌主要通过TLR2被人类单核细胞识别。在此，我们使用配体特异性阻断抗体表明，甘露糖受体（MR）作为未被调理的铜绿假单胞菌的吞噬受体，在人类单核细胞对铜绿假单胞菌感染产生促炎细胞因子的过程中，对TLR2的作用相同。两种受体的协同作用完全控制免疫反应。活的铜绿假单胞菌可激活核因子κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路，并增强在转染了MR的人胚肾293细胞中TLR2介导的信号传导。此外，在人类巨噬细胞被铜绿假单胞菌体内感染期间，MR与TLR2具有相同的动力学变化，并在内体中共定位。这些研究首次证明了MR与TLR2协同作用，在激活对铜绿假单胞菌感染的促炎反应中发挥重要作用。
