Phagocytic Receptors Activate Syk and Src Signaling during Borrelia burgdorferi PEhagocytosis
Phagocytic Receptors Activate Syk and Src Signaling during Borrelia burgdorferi PEhagocytosis
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DOI：
10.1128/iai.00004-17
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发表时间：
2017-10-01
影响因子：
3.1
通讯作者：
Petnicki-Ocwieja, Tanja
中科院分区：
文献类型：
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作者：
Killpack, Tess L.;Ballesteros, Maria;Petnicki-Ocwieja, Tanja
莱姆病病原体伯氏疏螺旋体的吞噬作用已被证明是对病原体产生炎症反应的重要因素。因此，了解吞噬作用的机制一直是莱姆病领域的一个非常感兴趣的领域。一些参与伯氏疏螺旋体吞噬的细胞表面受体已被报道，包括清道夫受体MARCO和整合素α 3 β 1。我们试图确定这些受体介导吞噬的机制，并确定与伯氏疏螺旋体接触后这些受体下游激活的信号通路。我们发现Syk和Src信号通路都参与了伯氏疏螺旋体的吞噬和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β 1都在Src激酶途径的激活中发挥作用。然而，只有整合素β 1参与了Syk的激活。有趣的是，整合素在没有信号适配器Dap12或FcR γ的帮助下激活Syk。因此，我们报道了多种途径参与伯氏疏螺旋体的内化，不同的细胞表面受体同时合作和独立地介导吞噬作用。
Phagocytosis of the Lyme disease-causing pathogen Borrelia burgdorferi 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 B. burgdorferi phagocytosis have been reported, including the scavenger receptor MARCO and integrin alpha 3 beta 1. 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 B. burgdorferi. We identified both Syk and Src signaling pathways as ones that participate in B. burgdorferi phagocytosis and the resulting cytokine activation. In our studies, we found that both MARCO and integrin beta 1 play a role in the activation of the Src kinase pathway. However, only integrin beta 1 participates in the activation of Syk. Interestingly, the integrin activates Syk without the help of the signaling adaptor Dap12 or FcR gamma. Thus, we report that multiple pathways participate in B. burgdorferi internalization and that different cell surface receptors act simultaneously in cooperation and independently to mediate phagocytosis.