Mus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA390724 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:IL-4 drives expansion of Th2 cells that cause generation of alternatively activated macrophages (AAMs). Filarial infections are established early in life, induce increased IL-4 production are co-endemic with tuberculosis (TB). We sought to understand, therefore, how mycobacteria are handled in the context of IL-4-induced AAM. Comparing IL-4 generated in vitro monocyte derived human AAMs to LPS and IFN-γ generated classically macrophages (CAMs), both infected with mycobacteria (BCG), we demonstrated increased early BCG uptake and increased IL-10 production in AAMs compared to CAMs. We further demonstrated that increased IL-10 production is mediated by upregulation of tumor progression locus 2 (TPL-2), an upstream activator of extracellular signal related kinases (ERKs) in AAMs but not in CAMs, both at the transcript as well as the protein level. Pharmacologic inhibition of TPL-2 significantly diminished IL-10 production only in BCG-infected AAMs. Finally, we validated our findings in an in vivo C57Bl/6 model of filarial infection, where an exaggerated Th2 induced lung-specific alternative activation led to TPL-2 and IL-10 upregulation on subsequent TB infection. These data show that in response to mycobacterial infection, IL-4 generated AAMs in chronic filarial infections have impaired immune responses to TB infection by increasing IL-10 production in a TPL-2 mediated manner. Experimental rationale (microarray): To understand the effect of a pre-existing filiarial infection on the immune response of mice to Mycobacterium tuberculosis
2017-06-17 | GSE100105 | GEO
Project description:Murine alternatively activated macrophages can exert anti-inflammatory effects. Expanding upon this, we sought to determine the ability of human IL-4-treated macrophages (i.e. hM(IL4)) to promote epithelial wound repair and serve as a novel anti-inflammatory cell transfer treatment for inflammatory bowel disease (IBD). Blood monocytes from healthy volunteers and patients with Crohn’s disease or ulcerative colitis (active and inactive disease) were converted to macrophages and treated with IL-4. Subsequently, cells were assessed by qPCR, in in vitro epithelial wounding and permeability models, and for anti-colitic capacity in dinitrobenzene sulphonic acid (DNBS)-treated Rag1-/- mice. IL-4 treatment of blood-derived macrophages from healthy volunteers and patients with inactive IBD resulted in a characteristic CD206+CCL18+CD14low/- phenotype (RNA-seq revealed IL-4 affected expression of 996 genes). Conditioned media from freshly generated or cryopreserved hM(IL4)s were equally effective in promoting wound healing, and reducing cytokine-driven loss of epithelial barrier function in vitro. Systemic delivery of hM(IL4) to DNBS-treated Rag1-/- mice significantly reduced disease as assessed my macroscopic disease and histopathology scores. Remarkably, the anti-colitic effect of hM(IL4) transfer was still apparent when mice were challenged with DNBS one month after receiving hM(IL4)s. Positing that hM(IL4)s would be anti-colitic, this study demonstrates the capacity of M(IL4)s from healthy volunteers and patients with inactive IBD to promote epithelial recovery after injury and to suppress colitis. These novel findings with hM(IL4), provide proof-of-concept support for the development of autologous M(IL4) transfer as a cellular immunotherapy for IBD.
2019-12-16 | GSE132732 | GEO
Project description:Macrophage activation must be tightly controlled to prevent overzealous responses that cause self-damage. MicroRNAs have been shown to promote classical macrophage activation by blocking concomitant anti-inflammatory signals and transcription factors, but can also place restraints on activation by preventing excessive TLR-signalling. In contrast, the microRNA profile associated with alternatively activated macrophages and their role in regulating wound-healing or anti-helminthic responses has not yet been described. Utilizing an in vivo model of alternative activation, in which adult Brugia malayi nematodes are surgically implanted in the peritoneal cavity of mice, we examined the profile of microRNA expression in these alternatively activated macrophages and compared this to alternatively activated IL-4 receptor knockout macrophages and thioglycollate elicited macrophages. Peritoneal macrophages from BALB/c wild type or IL-4 receptor knockout mice were elicited with thioglycollate or using nemtodes (peritoneal implant of Brugia malayi). The latter leads to a population of alternatively activated macrophages. Microarray analysis was used to examine the microRNA profile of WT alternatively activated macrophages (n = 4), IL-4 receptor knockout alternatively activated macrophages (n = 4), WT thioglycollate elicited macrophages (n = 3) and IL-4 receptor knockout thioglycollate elicited macrophages (n = 3).
2012-08-07 | E-GEOD-35047 | biostudies-arrayexpress
Project description:Papillomatous digital dermatitis (PDD) is a polymicrobial infection in soft tissue adjacent to the hoof and is the leading cause of lameness in dairy cattle. Treponema phagedenis-like (TPL) spirochetes are a constant feature of PDD lesions and are localized deep in infected tissue. Host-cell response mechanisms to TPL bacteria are poorly understood. To assess how bovine macrophages respond to cellular constituents of TPL spirochetes, changes in transcription were analyzed using serial analysis of gene expression (SAGE) and real time RT-PCR. This analysis revealed that bovine macrophages responded to stimulation with TPL-lysates by induction of several pro-apoptotic genes. Although several proinflammatory cytokines (eg. IL-6 and IL-8) are induced in treated macrophages, receptors and their accessory proteins for IL-1, IL-6, and IL-11 are either down regulated or unchanged. Surprisingly, IL-1beta is not induced and IL-18 is suppressed in treated macrophages. Two genes encoding proteins having negative effects on NFκB, IκB and Siva-1, are significantly induced in stimulated cells. Combined, these data suggest that the innate immune response of bovine macrophages exposed to TPL cellular constituents are impaired thereby enabling bacteria to resist clearance and induce lesion formation. Keywords: Bovine macrophage, transcription response, spirochete bacteria
2007-06-22 | GSE6702 | GEO
Project description:Background: Obesity is associated with infiltration of macrophages into adipose tissue. Adipose macrophages may contribute to an elevated inflammatory status by secreting a variety of pro-inflammatory mediators, including TNFalpha and IL-6. Recent data suggest that during diet-induced obesity the phenotype of adipose-resident macrophages changes from alternatively activated macrophages towards a more classical and pro-inflammatory phenotype. Here, we explore the effect of PPARγ-activation on obesity-induced inflammation in 129SV mice fed a high fat diet for 20 weeks. High fat feeding increased bodyweight gain, adipose tissue mass and liver triglycerides. Rosiglitazone treatment further increased adipose mass, reduced liver triglycerides and changed adipose tissue morphology towards smaller adipocytes. Surprisingly, rosiglitazone markedly increased the number of macrophages in adipose tissue, as shown by immunohistochemical analysis and quantification of macrophage marker genes CD68 and F4/80+. In adipose tissue, markers for classically activated macrophages including IL-18 were down regulated whereas markers characteristic for alternatively activated macrophages (Arginase 1, IL-10) were up regulated by rosiglitazone. Importantly, conditioned media from rosiglitazone-treated alternatively activated macrophages neutralized the inhibitory effect of macrophages on 3T3-L1 adipocyte differentiation, suggesting that alternatively activated macrophages may be involved in mediating the effects of rosiglitazone on adipose tissue morphology and mass. Our results suggest that short term rosiglitazone treatment increases infiltration of alternatively activated macrophages in adipose tissue. The alternatively activated macrophages might play a role in PPARγ-dependent expansion and remodeling of adipose tissue. Keywords: metabolic state analysis
2008-04-29 | GSE11295 | GEO
Project description:Background: Obesity is associated with infiltration of macrophages into adipose tissue. Adipose macrophages may contribute to an elevated inflammatory status by secreting a variety of pro-inflammatory mediators, including TNFalpha and IL-6. Recent data suggest that during diet-induced obesity the phenotype of adipose-resident macrophages changes from alternatively activated macrophages towards a more classical and pro-inflammatory phenotype. Here, we explore the effect of PPARγ-activation on obesity-induced inflammation in 129SV mice fed a high fat diet for 20 weeks. High fat feeding increased bodyweight gain, adipose tissue mass and liver triglycerides. Rosiglitazone treatment further increased adipose mass, reduced liver triglycerides and changed adipose tissue morphology towards smaller adipocytes. Surprisingly, rosiglitazone markedly increased the number of macrophages in adipose tissue, as shown by immunohistochemical analysis and quantification of macrophage marker genes CD68 and F4/80+. In adipose tissue, markers for classically activated macrophages including IL-18 were down regulated whereas markers characteristic for alternatively activated macrophages (Arginase 1, IL-10) were up regulated by rosiglitazone. Importantly, conditioned media from rosiglitazone-treated alternatively activated macrophages neutralized the inhibitory effect of macrophages on 3T3-L1 adipocyte differentiation, suggesting that alternatively activated macrophages may be involved in mediating the effects of rosiglitazone on adipose tissue morphology and mass. Our results suggest that short term rosiglitazone treatment increases infiltration of alternatively activated macrophages in adipose tissue. The alternatively activated macrophages might play a role in PPARγ-dependent expansion and remodeling of adipose tissue. Keywords: metabolic state analysis Pure bred wild-type (129S1/SvImJ) male mice received a low fat diet or high fat diet for 21 weeks, providing 10 or 45% energy percent in the form of triglycerides (D12450B or D12451, Research Diets, New Brunswick, USA). The lard component in these diets was replaced by palm oil. In the last week of diet intervention, half of the mice receiving the HFD were switched to HFD supplemented with Rosiglitazone (0.01 % wt/wt). Animals were sacrificed in the fed state. Epididymal adipose tissue was excised and frozen in liquid nitrogen. Pooled RNA samples from 5 mice per experimental group were used for microarray analysis. Samples were hybridized on Affymetrix GeneChip Mouse Genome 430-2.0 plus arrays. Five microgram total RNA was labelled according to the Affymetrix One-cycle Target Labeling Assay, fragmented and hybridized according to Affymetrix's protocols.
2008-04-29 | E-GEOD-11295 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE16385: Expression data from human macrophages GSE16386: Expression data from human alternatively activated macrophages GSE25088: PPARg and IL-4-induced gene expression data from wild-type and STAT6 knockout mouse bone marrow-derived macrophages GSE25123: PPARg and IL-4-induced gene expression data from PPARg +/- LysCre and PPARg fl/- LysCre mouse bone marrow-derived macrophages GSE25125: PPARg and IL-4-induced gene expression data from PPARg +/- LysCre and PPARg fl/- LysCre mouse bone marrow-derived alternatively activated macrophages and immature dendritic cells (iDCs) Refer to individual Series
2010-11-18 | E-GEOD-16387 | biostudies-arrayexpress
Project description:Conditional macrophage-specific PPARg knockout mice were generated on C57Bl/6 background by breeding PPARg fl/- (one allele is floxed, the other is null) and lysozyme Cre transgenic mice. PPARg and IL-4 signaling was analyzed on bone marrow-derived macrophages. Bone marrow of 4 mice per group was isolated and differentiated to alternatively activated macrophages with 20 ng/ml M-CSF and 20 ng/ml IL-4 or to iDCs with 20 ng/ml GM-CSF+20 ng/ml IL-4. 1 uM Rosiglitazone (RSG) was used to activate PPARg. From each mouse 4 samples were generated: 1. M-CSF+IL-4, 2. M-CSF+IL-4+RSG, 3. GM-CSF+IL-4 and 4. GM-CSF+IL-4+RSG. All compounds were added throughout the whole differentiation process, and fresh media was added every other day. Control cells were treated with vehicle (DMSO:ethanol). After 9 days, RNA was isolated and gene expression profiles were analyzed using ABI Mouse Genome Survey Arrays. 4 PPARg +/- LysCre and 4 PPARg fl/- LysCre mice were used to isolate bone marrow and from each alternatively activated macrophages were differentiated with IL-4 and simultaneously treated with vehicle or RSG, iDCs were differentiated with GM-CSF+IL-4 and simultaneously treated with vehicle or RSG. Altogether we analyzed 32 samples with 4 biological replicates as below.
2010-11-18 | E-GEOD-25125 | biostudies-arrayexpress
Project description:We used microarrays to find Stat6 dependent genes in control and IL-4 exposed bone marrow derived macrophages. Alternatively activated macrophages (AAM) accumulate in tissues during Th2-associated immune responses like helminth infections and allergic disorders. These cells possess potent inhibitory activity against T cells. The differentiation of AAM depends on IL-4/IL-13-mediated activation of the transcription factor Stat6. Stat6 is also required in AAM to induce several genes, such as YM1, FIZZ1 and Arginase1.
2010-07-19 | GSE20030 | GEO