Merritt Peter M, Nero Thomas, Bohman Lesley, Felek Suleyman, Krukonis Eric S, Marketon Melanie M
Department of Biology, Indiana University, Bloomington, IN, USA.
Cell Microbiol. 2015 May;17(5):666-87. doi: 10.1111/cmi.12391. Epub 2014 Nov 25.
Yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type III secretion system. Yet, the mechanism for target cell selection remains a mystery. Here we investigate the interaction of Yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. We find that interactions with primary immune cells rely on multiple factors. First, the bacterial adhesin Ail is required for efficient targeting of neutrophils in vivo. However, Ail does not appear to directly mediate binding to a specific cell type. Instead, we find that host serum factors direct Y. pestis to specific innate immune cells, particularly neutrophils. Importantly, specificity towards neutrophils was increased in the absence of bacterial adhesins because of reduced targeting of other cell types, but this phenotype was only visible in the presence of mouse serum. Addition of antibodies against complement receptor 3 and CD14 blocked target cell selection, suggesting that a combination of host factors participate in steering bacteria towards neutrophils during plague infection.
耶尔森菌属在感染过程中表现出对淋巴组织的嗜性，并且这些细菌通过III型分泌系统选择固有免疫细胞来递送细胞毒性效应物。然而，靶细胞选择的机制仍然是个谜。在这里，我们研究了鼠疫耶尔森菌与小鼠脾细胞的相互作用，以确定参与靶向过程的因素。我们发现与原代免疫细胞的相互作用依赖于多种因素。首先，细菌粘附素Ail是体内有效靶向中性粒细胞所必需的。然而，Ail似乎并不直接介导与特定细胞类型的结合。相反，我们发现宿主血清因子将鼠疫耶尔森菌导向特定的固有免疫细胞，特别是中性粒细胞。重要的是，由于对其他细胞类型的靶向减少，在没有细菌粘附素的情况下对中性粒细胞的特异性增加，但这种表型仅在存在小鼠血清时可见。添加针对补体受体3和CD14的抗体可阻断靶细胞选择，这表明在鼠疫感染期间，多种宿主因子共同参与将细菌导向中性粒细胞。
