Delineate innate immune responses in populations at risk (the elderly and the immunosuppressed) that are different from the general population

We will assess the efficiency of the immune response of monocytes and dendritic cells in different populations (young adult and elderly) in response to stimulation with specific TLR ligands. We will focus separately on TLRs 3, 7, 8, 9, that recognize viral targets, TLRs 1, 2, 4, 6 (bacterial targets), and the effects of aging on MIF.

We will quantify TLR expression as well as efficiency of signaling pathways triggered by TLR engagement to identify mechanisms that contribute to the impairments of innate immunity associated with aging and immunosuppression.

Finally, we will assess the functional and genetic polymorphisms of MIF in the innate response to TLR stimulation.

本研究拟评估不同人群（青年成年人与老年群体）的单核细胞及树突状细胞在经特定Toll样受体（Toll-like receptor, TLR）配体刺激后的免疫应答效率。本研究将分别聚焦识别病毒靶标的TLR3、7、8、9，识别细菌靶标的TLR1、2、4、6，以及衰老对巨噬细胞迁移抑制因子（Macrophage Migration Inhibitory Factor, MIF）的影响。我们将定量检测TLR的表达水平，以及TLR结合后触发的信号通路的激活效率，以阐明与衰老及免疫抑制相关的固有免疫功能损伤的潜在机制。最后，本研究将评估MIF在TLR刺激介导的固有免疫应答中的功能与遗传多态性。