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Cellular Mechanisms of the Adjuvant Activity of the Flagellin Component FljB of Salmonella enterica Serovar Typhimurium To Potentiate Mucosal and Systemic Responses

机译:肠炎沙门氏菌鼠伤寒鞭毛蛋白组分FljB佐剂活性增强粘膜和全身反应的细胞机制

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An expanding area of interest is the utilization of microbe-based components to augment mucosal and systemic immune responses to target antigens. Thus, the aim of the present study was to assess if the flagellin component FljB from Salmonella enterica serovar Typhimurium could act as a mucosal adjuvant and then to determine the cellular mechanism(s) by which FljB mediates its adjuvant properties. To determine if FljB could act as a mucosal adjuvant, mice were immunized by the intranasal (i.n.) route with antigen alone or in conjunction with FljB. Additionally, we assessed how FljB affected the levels of the costimulatory molecules B7-1 and B7-2 on dendritic cells by flow cytometry and determined the functional role these costimulatory molecules played in the adjuvant properties of FljB in vivo. Mice immunized by the i.n. route with antigen and FljB exhibited significantly elevated levels of mucosal and systemic antibody and CD4+-T-cell responses compared to mice given antigen only. Stimulation of dendritic cells in vitro with FljB resulted in a pronounced increase in the surface expression of B7-1 and B7-2. The percentage of dendritic cells expressing B7-2 but not B7-1 increased significantly when stimulated with FljB over a concentration range of 10 to 10,000 ng/ml. Immunization of wild-type and B7-1, B7-2, and B7-1/2 knockout mice by the i.n. route revealed that the ability of FljB to increase B7-2 expression is largely responsible for its adjuvant effect in vivo. These findings demonstrate that FljB can act as an effective mucosal adjuvant and that its ability to enhance the level of B7-2 expression is predominantly responsible for its adjuvant properties.
机译:关注的扩展领域是利用基于微生物的成分来增强对靶抗原的粘膜和全身免疫应答。因此,本研究的目的是评估肠沙门氏菌鼠伤寒沙门氏菌鞭毛蛋白组分FljB是否可以作为粘膜佐剂,然后确定FljB介导佐剂的细胞机制。属性。为了确定FljB是否可以充当粘膜佐剂,通过鼻内(i.n.)途径用单独的抗原或与FljB结合的抗原免疫小鼠。此外,我们通过流式细胞术评估了FljB如何影响树突状细胞上共刺激分子B7-1和B7-2的水平,并确定了这些共刺激分子在体内FljB佐剂特性中的功能。经i.n.免疫的小鼠与仅给予抗原的小鼠相比,抗原和FljB的免疫途径表现出显着升高的粘膜和全身抗体水平以及CD4 + -T细胞反应。 FljB在体外刺激树突状细胞导致B7-1和B7-2的表面表达明显增加。当在浓度范围为10至10,000 ng / ml的FljB中刺激时,表达B7-2但不表达B7-1的树突状细胞的百分比显着增加。 i.n.免疫野生型和B7-1,B7-2和B7-1 / 2敲除小鼠。该途径揭示了FljB增加B7-2表达的能力在很大程度上是其体内佐剂作用的原因。这些发现证明FljB可以充当有效的粘膜佐剂,并且其增强B7-2表达水平的能力主要对其佐剂性质负责。

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