Macrophage polarization in the regulation of immune functions

本课题组研究了病毒感染过程中巨噬细胞（Mf）的免疫生物学。这些吞噬细胞是免疫系统中至关重要的细胞，因为它们在先天免疫和适应性免疫中都起着核心作用。根据感染类型的不同，Mf可以极化为M1或M2细胞，这是由其特定的表型和功能标记所定义的。促炎M1表型是由干扰素γ (IFN?)存在下的脂多糖（LPS）诱导的，而M2 Mf则是在IL-4细胞因子刺激后产生的，其抗炎特性众所周知。在这个更新应用和我们最近的发现的基础上，我们将研究小鼠Mf极化成M1或M2如何在病毒与宿主相互作用期间调节免疫系统，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很容易极化成M1或M2 Mf，它们的细胞因子谱不同。因此，我们假设极化Mf将表现出对病毒感染的易感性改变。此外，这些M1和M2 Mf将通过直接和交叉呈递途径处理病毒抗原，对CD8+ T细胞具有不同的效率，从而产生独特的CD8+ T细胞激活特征。******本提案的具体目标如下：***1)确定极化Mf如何处理病毒感染（1-4年级），理学硕士学生#1和3。***2)定义极化Mf（1-5年级）如何影响LCMV抗原对CD8+ T细胞的抗原呈递（直接和交叉）。***3)研究极化Sp-Mf如何调节记忆CD8+ T细胞的激活（2-5年级），硕士学生#2和4。**********总体而言，本文描述的研究应进一步确定Mf极化，特别是来自脾脏的Mf如何在病毒-免疫系统相互作用期间影响多种免疫参数。我们相信，除了在这个非常关键的研究领域培养下一代加拿大科学家外，我们提出的实验结果将为极化Mf对病原体识别的调节提供深刻的新见解。推进这项研究的学生不仅将获得操作细胞和病毒免疫学关键仪器的宝贵技术知识，而且还将成为称职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.**