Killpack Tess L, Ballesteros Maria, Bunnell Stephen C, Bedugnis Alice, Kobzik Lester, Hu Linden T, Petnicki-Ocwieja Tanja
Department of Biological Sciences, Wellesley College, Wellesley, Massachusetts, USA.
Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA.
Infect Immun. 2017 Sep 20;85(10). doi: 10.1128/IAI.00004-17. Print 2017 Oct.
Phagocytosis of the Lyme disease-causing pathogen has been shown to be important for generating an inflammatory response to the pathogen. As a result, understanding the mechanisms of phagocytosis has been an area of great interest in the field of Lyme disease. Several cell surface receptors that participate in phagocytosis have been reported, including the scavenger receptor MARCO and integrin α3β1. We sought to define the mechanisms by which these receptors mediate phagocytosis and to identify signaling pathways activated downstream of these receptors upon contact with We identified both Syk and Src signaling pathways as ones that participate in phagocytosis and the resulting cytokine activation. In our studies, we found that both MARCO and integrin β1 play a role in the activation of the Src kinase pathway. However, only integrin β1 participates in the activation of Syk. Interestingly, the integrin activates Syk without the help of the signaling adaptor Dap12 or FcRγ. Thus, we report that multiple pathways participate in internalization and that different cell surface receptors act simultaneously in cooperation and independently to mediate phagocytosis.
吞噬导致莱姆病的病原体已被证明对于产生针对该病原体的炎症反应很重要。因此，了解吞噬作用机制一直是莱姆病领域非常感兴趣的一个方面。已经报道了几种参与吞噬作用的细胞表面受体，包括清道夫受体MARCO和整合素α3β1。我们试图确定这些受体介导吞噬作用的机制，并确定与病原体接触后这些受体下游激活的信号通路。我们确定Syk和Src信号通路均参与吞噬作用以及由此产生的细胞因子激活。在我们的研究中，我们发现MARCO和整合素β1在Src激酶途径的激活中均发挥作用。然而，只有整合素β1参与Syk的激活。有趣的是，整合素在没有信号衔接蛋白Dap12或FcRγ的帮助下激活Syk。因此，我们报道多种途径参与内化，并且不同的细胞表面受体同时协同且独立地发挥作用以介导吞噬作用。
