Macrophage polarization in the regulation of immune functions

我们的研究小组调查了病毒感染期间巨噬细胞(MF)的免疫生物学。这些吞噬细胞是免疫系统中的关键细胞，因为它们在先天免疫和获得性免疫中都发挥着核心作用。根据感染类型的不同，MF可以分化为M1或M2细胞，这是由其特定的表型和功能标记定义的。促炎症的M1表型是在干扰素-γ存在的情况下由脂多糖(LPS)诱导的，而以抗炎特性而闻名的M2 MF是在IL-4细胞因子刺激后发展起来的。在这一新的应用和我们最新发现的基础上，我们将研究小鼠MF极化为M1或M2在病毒与宿主相互作用期间如何调节免疫系统，无论是在体外还是在体内。*我们总体长期目标的基本前提是，像Sp-MF这样的MF很容易两极分化为M1或M2 MF，这两种MF的细胞因子谱不同。因此，我们假设极化的MF将表现出对病毒感染的改变的易感性。此外，这些M1和M2 MF将通过直接和交叉递呈途径处理病毒抗原，对CD8+T细胞的效率不同，从而产生独特的CD8+T细胞激活信号。*这项建议的具体目标如下：*1)确定极化的MF如何应对病毒感染(1-4年级)，理科学生#1和3。*2)定义极化的MF(1-5年级)博士生#1如何影响LCMV抗原向CD8+T细胞的抗原递送(直接和交叉)。*3)研究极化的Sp-MF如何调节记忆CD8+T细胞的激活(2-5年级)，理科学生#2和4。*这里描述的研究应该进一步确定在病毒-免疫系统相互作用过程中，MF极化，特别是来自脾的MF如何影响多个免疫参数。我们相信，除了在这一非常关键的研究领域培训下一代加拿大科学家外，我们拟议的实验结果将为极化MF对病原体识别的调控提供深刻的新颖见解。推进这项研究的学生不仅将在操作用于细胞和病毒免疫学的关键仪器方面获得宝贵的技术专业知识，而且他们还将成为有能力的沟通者和独立的项目经理。

Our research group investigates the immunobiology of macrophages (Mf) during viral infection. These phagocytes are crucial cells in the immune system because they play a central role in both innate and adaptive immunity. Depending on the type of infection, Mf can polarize into either M1 or M2 cells as defined by their specific phenotypic and functional markers. The pro-inflammatory M1 phenotype is induced by lipopolysaccharide (LPS) in the presence of interferon-gamma (IFN?), whereas M2 Mf known for their anti-inflammatory properties develop after IL-4 cytokine stimulation. In this renewal application and building on our recent discoveries, we will investigate how murine Mf polarization into either M1 or M2 can regulate the immune system during virus-host interactions, both in vitro and in vivo. ******The fundamental premise for our overarching long-term goal is that Mf such as Sp-Mf are readily polarized into either M1 or M2 Mf, which differ in their cytokine profile. Therefore, we hypothesize that polarized Mf will exhibit altered susceptibility to virus infection. Furthermore, these M1 and M2 Mf will process viral antigens via the direct and cross-presentation pathways with disparate efficiencies to CD8+ T cells, resulting in unique CD8+ T cell activation signatures. ******The specific aims for this proposal are as follows:***1) Determine how polarized Mf deal with virus infection (years 1-4), MSc student #1 & 3.***2) Define how antigen presentation (direct and cross) of LCMV antigens to CD8+ T cells are affected by the polarized Mf (years 1-5) PhD student #1. ***3) Investigate how polarized Sp-Mf regulate memory CD8+ T cells activation (years 2-5), MSc students #2 & 4.**********Overall, the studies described here should further identify how Mf polarization especially Mf derived from the spleen can influence multi-immune parameters during virus-immune system interactions. We are confident that, in addition to training the next generation of Canadian scientists in this very critical research field, the results of our proposed experiments will provide profound novel insights concerning the regulation of pathogen recognition by polarized Mf. The students who advance this research will not only obtain invaluable technical expertise in operating key instruments used in cellular and viral immunology, but they will also become competent communicators and independent project managers.**