Center for Inflammatory and Infectious Diseases, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA.
Cell Microbiol. 2011 Apr;13(4):620-34. doi: 10.1111/j.1462-5822.2010.01558.x. Epub 2010 Dec 28.
Inhalational anthrax is initiated by pulmonary exposure to Bacillus anthracis spores. Spore entry into lung epithelial cells is observed both in vitro and in vivo and evidence suggests it is important for bacterial dissemination and virulence. However the specific host receptor and spore factor that mediate the entry process were unknown. Here, we report that integrin α2β1 is a major receptor for spore entry. This is supported by results from blocking antibodies, siRNA knock-down, colocalization, and comparison of spore entry into cells that do or do not express α2. BclA, a major spore surface protein, is found to be essential for entry and α2β1-mediated entry is dependent on BclA. However, BclA does not appear to bind directly to α2. Furthermore, spore entry into α2-expressing cells is dramatically reduced in the absence of serum, suggesting that additional factors are involved. Finally, complement component C1q, also an α2β1 ligand, appears to act as a bridging molecule or a cofactor for BclA/α2β1-mediated spore entry and BclA binds to C1q in a dose-dependent and saturable manner. These findings suggest a novel mechanism for pathogen entry into host cells as well as a new function for C1q-integrin interactions. The implications of these findings are discussed.
吸入性炭疽病是由肺部接触炭疽芽孢杆菌孢子引起的。在体外和体内都观察到孢子进入肺上皮细胞，这表明它对细菌传播和毒力很重要。然而，介导进入过程的特定宿主受体和孢子因子尚不清楚。在这里，我们报告整合素α2β1 是孢子进入的主要受体。这一结果得到了阻断抗体、siRNA 敲低、共定位以及比较不表达α2 的细胞和表达α2 的细胞中孢子进入的结果的支持。BclA 是一种主要的孢子表面蛋白，对于进入是必不可少的，并且α2β1 介导的进入依赖于 BclA。然而，BclA 似乎不直接与α2 结合。此外，在没有血清的情况下，α2 表达细胞中的孢子进入显著减少，这表明还涉及其他因素。最后，补体成分 C1q 也是α2β1 的配体，似乎作为桥连分子或 BclA/α2β1 介导的孢子进入的辅助因子起作用，并且 BclA 以剂量依赖和饱和的方式与 C1q 结合。这些发现表明了病原体进入宿主细胞的一种新机制，以及 C1q-整合素相互作用的新功能。讨论了这些发现的意义。
