巨噬细胞是自身免疫系统感应细菌入侵的主要细胞，通过激活产生炎症细胞因子来协调免疫反应。葡萄糖是与该过程最相关的代谢燃料，然而胰岛素在调控巨噬细胞炎症反应中的作用目前仍不明确。这里我们提出一个创新的设想：即与代谢组织相反，胰岛素和炎症信号通路可以在激活的巨噬细胞中发生协同作用，从而协调巨噬细胞的葡萄糖利用和炎症反应。我们推测一种名为BCAP的接头蛋白是这种协同作用的关键调控因子，并将从BCAP着手，探究这种协同作用的调控机制和生理相关性。相反，巨噬细胞胰岛素抵抗与肥胖相关的代谢疾病中巨噬细胞功能受损和宿主防御缺失密切相关，我们认为其根本基础可能是炎症信号和胰岛素信号的协同失调。综上，我们的研究将推动形成一个独特的概念和实验结构，以解释在细菌感染期间，有限的能量资源是如何从存储在代谢组织转向被激活的免疫细胞利用，并为探索治疗感染期间的炎症反应和肥胖相关的代谢疾病提供新的分子靶点。

During microbial infection, macrophages of the innate immune system respond to microbial sensing by becoming activated to produce inflammatory cytokines that coordinate the immune response. Such macrophage activation is energetically costly and must be fueled by increased glucose metabolism, but whether insulin influences such glucose metabolism to regulate induction of inflammatory responses in activated macrophages is not known. Here we propose the innovative hypothesis that, in contrast to metabolic tissues, inflammatory signaling and insulin signaling synergize to increase glucose utilization in activated macrophages, thus allowing for optimal induction and suppression of inflammatory responses. We propose that an adaptor protein called BCAP regulates such synergy between inflammatory signaling and insulin signaling, and will investigate the mechanistic regulation and physiological relevance of such synergy. Conversely, macrophage insulin resistance has been linked to impaired macrophage functions and host defense in obesity-associated metabolic diseases, and we propose that an underlying basis could be the dysregulation of synergy between inflammatory signaling and insulin signaling. Successful completion of our proposed studies would advance a unique framework for understanding how limiting metabolic resources are prioritized during infection, away from storage in metabolic tissues towards activated immune cells, and provide new molecular targets that could be explored for therapeutic modulation of inflammatory responses during infection and obesity-associated metabolic diseases.