Macrophage polarization in the regulation of immune functions

点击翻译按钮获取中文摘要

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.**