Project description:Myeloid cells are prominent cellular constituents of the CNS. Under physiologic conditions, these include microglia within the parenchyma and systemic compartment derived macrophages localized to the perivascular spaces. Defining the relative distribution and functions of microglia versus blood-derived macrophages in the CNS parenchyma under pathologic conditions remains a challenge due to limitations in being able to distinguish these cell types. Approaches to distinguishing microglia and macrophages in experimental models include use of chimeric and parabiotic animals and molecular genetic techniques to selectively differentially label or delete a specific cell type. The current report will compare gene expression of human microglia and macrophages under distinct states of activation or “polarization” and relate these to their roles in tissue injury and protection /repair in the central nervous system (CNS). We used Affymetrix Human Gene HT 2.0 microarrays to compare whole transcriptomes of microglia and macrophages under defined polarization conditions.
Project description:Myeloid cells are prominent cellular constituents of the CNS. Under physiologic conditions, these include microglia within the parenchyma and systemic compartment derived macrophages localized to the perivascular spaces. Defining the relative distribution and functions of microglia versus blood-derived macrophages in the CNS parenchyma under pathologic conditions remains a challenge due to limitations in being able to distinguish these cell types. Approaches to distinguishing microglia and macrophages in experimental models include use of chimeric and parabiotic animals and molecular genetic techniques to selectively differentially label or delete a specific cell type. The current report will compare gene expression of human microglia and macrophages under distinct states of activation or “polarization” and relate these to their roles in tissue injury and protection /repair in the central nervous system (CNS). We used Affymetrix Human Gene HT 2.0 microarrays to compare whole transcriptomes of microglia and macrophages under defined polarization conditions.
Project description:Infiltrating monocyte derived macrophages (MDMs) and resident microglia dominate CNS injury sites. We show that MDMs and microglia can directly communicate to modulate each other’s function. Also, the presence of MDMs in CNS injury suppresses microglia-mediated phagocytosis and inflammation. We suggest that macrophages infiltrating the injured CNS provide a mechanism to control acute and chronic microglia-mediated inflammation, which could otherwise drive damage in a variety of CNS conditions. To understand the global effects of macrophage communication to microglia, we transcriptionally profiled activated adult mouse microglia in the presence or absence of macrophages with and without an inflammatory stiumulus (LPS)
Project description:Microglia isolated from glioma patients gain anti-tumor activities upon poly (I:C) stimulation. Expression profiles of human tumor-infiltrating microglia/macrophages before (untreated) and after treatment with poly (I:C) for 48h (induced). Tumor-infiltrating microglia/macrophages were isolated from freshly excised brain tumors
Project description:Unstimulated (M0), M1-polarized (GM-CSF, LPS, IFNγ-stimulated), and M2-polarized (M-CSF, IL-4-stimulated) canine blood-derived macrophages were generated in vitro and investigated for differences in their transcriptome to create a basis for future investigations upon the role of macrophage polarization in dogs, a species, which has emerging importance for translational research.
Project description:in the present study we investigate polarized canine macrophages using transcriptome sequencing, a larger panel of flow cytometry markers, and antimicrobial functional assays. Transcriptome analysis of primary canine monocyte-derived macrophages revealed unique, previously unreported signatures for polarized M1 and M2 macrophages.
Project description:microRNAs are small non-coding RNAs that regulate gene expression at a post-translational level, and play a crucial role in the development of cells of the immune system. Macrophages are essential for generating inflammatory reactions upon tissue damage and encountering of invading pathogens, yet modulation of their immune responses is critical for maintaining tissue homeostasis. Macrophages can present different phenotypes, depending on the cytokine environment they encounter in the affected tissues. In this study, we have identified expression signatures of miRNAs that are differentially regulated during maturation of monocytes and polarization of macrophages by cytokines. We present a comprehensive characterization of miRNA expression in human monocytes and M1, M2a and M2c polarized macrophages, using next-generation Sequencing by Oligonucleotide Ligation and Detection (SOLiD). We have analyzed freshly isolated human monocytes and 5 day monocyte-derived macrophages unstimulated, or stimulated with IFNgamma+TNFalpha (M1), IL-4 (M2a) or IL-10 (M2c).