Project description:To investigate the plasticity of Lipolysaccharide (LPS) tolerance, we employed microarray profiling to analyse the gene expression profile in macrophage. Four macrophage populations were induced; Untreated macrophages (Control group), Acute response to LPS (LPS activation group), LPS tolerance (T – Tolerant group) and recovered (R = recovered macrophage group) Using transcriptional analysis we demonstrate that recovery from LPS tolerance (R – Recovery), as defined by cytokine gene expression, is associated with a global change in the transcriptional profile of macrophage. This data confirms that LPS tolerance is a transient state which results in induction of novel hybrid macrophage activation state with a unique transcriptional signature.
Project description:To investigate the plasticity of Lipolysaccharide (LPS) tolerance, we employed microarray profiling to analyse the gene expression profile in macrophage. Four macrophage populations were induced; Untreated macrophages (Control group), Acute response to LPS (LPS activation group), LPS tolerance (T – Tolerant group) and recovered (R = recovered macrophage group) Using transcriptional analysis we demonstrate that recovery from LPS tolerance (R – Recovery), as defined by cytokine gene expression, is associated with a global change in the transcriptional profile of macrophage. This data confirms that LPS tolerance is a transient state which results in induction of novel hybrid macrophage activation state with a unique transcriptional signature. Bone marrow derived macrophages were polarised into three activation states; Acute response to LPS (A), LPS tolerant (T) and recovered (R). Gene expression was measured at 4 hours post stimulation with LPS. Three independent experiments were performed to measure gene expression changes between each macrophage group.
Project description:ATAC-seq profiling of Nfat5 KO and wild type macrophages derived from bone marrow (primary cells), treated or not with Lipopolysaccharide (LPS).
Project description:Macrophage plasticity allows cells to adopt different phenotypes, a property with potentially important implications in chronic pulmonary disorders such as cystic fibrosis (CF). We examined the transcriptional and functional significance of macrophage repolarization from an “M1” (LPS-stimulated) towards an “M2” phenotype using 5 stimuli. We found that macrophages exhibit highly diverse responses to distinct M2-polarizing stimuli. Specifically, we observed that IL-10 abrogated LPS-tolerance allowing for rapid restoration of LPS responsiveness. In contrast, IL-4 enhanced LPS-tolerance, dampening pro-inflammatory responses after repeat LPS challenge. We found enrichment of phagocytosis-associated pathways in macrophages stimulated with IL-10, leading them to display the greatest efferocytosis ability. Finally, we observed that CF macrophages had intact reparative responses, suggesting that macrophage contributions to CF lung disease are shaped by their environmental milieu and are modifiable. These findings highlight the diversity of macrophage activation states, attribute functional consequences to these stimuli, and provide a unique resource of human macrophage repolarization markers.
Project description:We have employed whole genome microarray expression profiling to identify differently expressed genes following stimulation of wild-type bone-marrow derived macrophages with Escherichia coli lipopolysaccharide (LPS). Macrophages were stimulated with LPS (100 ng/ml) for 6 hours and a signature was identified that distinguished between infected and control samples. Expression of several genes from this signature was quantified in the same RNA samples by real-time PCR, confirming the predicted macrophage response pattern.
Project description:This SuperSeries is composed of the following subset Series: GSE19482: Transcriptional responses of human monocyte-derived macrophages (HMDM) to lipopolysaccharide (LPS) GSE19490: Transcriptional responses of mouse BMM and TEPM to lipopolysaccharide (LPS) GSE19765: Transcriptional responses of human monocyte-derived macrophages (HMDM) to lipopolysaccharide (LPS) - Illumina arrays GSE19766: Transcriptional responses of mouse bone marrow-derived macrophages (BMM) to lipopolysaccharide (LPS) - Illumina arrays Refer to individual Series
Project description:We have employed whole genome microarray expression profiling to identify differently expressed genes following stimulation of interleukin-16-knock-out bone-marrow derived macrophages with Escherichia coli lipopolysaccharide (LPS). Macrophages were stimulated with LPS (100 ng/ml) for 6 hours and a signature was identified that distinguished between infected and control samples. Expression of several genes from this signature was quantified in the same RNA samples by real-time PCR, confirming the predicted macrophage response pattern.
Project description:To provide a global perspective on the relationships between macrophage activation programs and to understand how certain pathogens circumvent them, we used transcriptional profiling by genome wide microarray analysis to compare the responses of mouse macrophages following exposure to the intracellular parasites Trypanosoma cruzi and Leishmania mexicana, the bacterial product lipopolysaccharide (LPS), and the cytokines IFNG, TNF, IFNB, IL-4, IL-10, and IL-17. We found that LPS induced a classical activation state that resembled macrophage stimulation by the Th1 cytokines IFNG and TNF. However, infection by the protozoan pathogen Leishmania mexicana produced so few transcriptional changes that the infected macrophages were almost indistinguishable from uninfected cells. Trypanosoma cruzi activated macrophages produced a transcriptional signature characterized by the induction of interferon-stimulated genes by 24 h post-infection. Despite this delayed IFN response by T. cruzi, the transcriptional response of macrophages infected by the kinetoplastid pathogens more closely resembled the transcriptional response of macrophages stimulated by the cytokines IL-4, IL-10, and IL-17 than macrophages stimulated by Th1 cytokines. Keywords: Bone marrow macrophage response to intracellular parasites and cytokines
Project description:Intestinal epithelial cells express the lipopolysaccharide (LPS) receptor Toll-like receptor (TLR4) and are responsive to LPS stimulation. Following LPS exposure, epithelial cells, similar to myeloid cells such as macrophages, acquire a state of tolerance. Innate immune tolerance is characterized by a lack of expression of proinflammatory genes in response to repeated stimulation. Tolerant epithelial cells, however, exhibit sustained expression of a distinct set of genes encoding for proteins involved in metabolism and homeostasis. This study comparatively analyzes the gene expression profile 6 hours after LPS stimulation (acute response) versus 6 hours LPS followed by 90 hours incubation in the absence of LPS (tolerant response).
Project description:We have employed whole genome microarray expression profiling to identify differently expressed genes following stimulation of interleukin-16-knock-out bone-marrow derived macrophages with Escherichia coli lipopolysaccharide (LPS). Macrophages were stimulated with LPS (100 ng/ml) for 6 hours and a signature was identified that distinguished between infected and control samples. Expression of several genes from this signature was quantified in the same RNA samples by real-time PCR, confirming the predicted macrophage response pattern. Gene expression in macrophages was measured at 6 hours after stimulation Three independent experiments were performed.