Transcriptional profiles of macrophages in resolving inflammation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE28621 | GEO | 2014/05/09
SECONDARY ACCESSION(S): PRJNA138723
REPOSITORIES: GEO
Similar Datasets
Project description:We have performed a comprehensive transcriptional analysis of specific monocyte and macrophage (MM-CM-^X) subsets during an acute self-resolving inflammatory insult. Following initial induction of acute inflammation, tissue resident (Resident) MM-CM-^X are rapidly M-bM-^@M-^XclearedM-bM-^@M-^Y from the inflammatory foci, only becoming recoverable as inflammation resolves. Monocytes are recruited to the inflammatory lesion where they differentiate into MM-CM-^X. We term these monocyte-derived MM-CM-^X M-bM-^@M-^Xinflammation-associatedM-bM-^@M-^Y to distinguish them from Resident MM-CM-^X which are present throughout the inflammatory response and can renew during the resolution of inflammation by proliferation. Comparative analysis of the Mo and MM-CM-^X populations (both M-bM-^@M-^Xinflammation-associatedM-bM-^@M-^Y and Resident MM-CM-^X) identifies select genes expressed in subsets of M-bM-^@M-^Xinflammation-associatedM-bM-^@M-^Y and Resident MM-CM-^X that play important roles in the resolution of inflammation and/or for immunity, including molecules involved in antigen presentation, cell cycle and others associated with M-bM-^@M-^XimmaturityM-bM-^@M-^Y and MM-CM-^X activation. We purified monocyte and macrophage populations from the peritoneal cavity of C57BL/6 mice 4, 18, 72 and 168 hours after the induction of inflammation with intraperitoneal administration of zymosan (2x10^7 particles). We also purified tissue resident macrophages and Ly-6B+ bone marrow monocytes from naive mice as reference populations.
2014-05-09 | E-GEOD-28621 | biostudies-arrayexpress
Project description:Molecular profiling of infiltrating monocyte-derived macrophages versus resident kupffer cells following acute liver injury The liver has a remarkable capacity to regenerate after injury; yet, the role of macrophages (MF) in this process remains controversial mainly due to difficulties in distinguishing between different MF-subsets. Here, we utilized a murine model of acute liver injury caused by overdose of acetaminophen (APAP) and defined three distinct MF subsets that populate the liver following injury. Accordingly, resident Kupffer cells (KC) were significantly reduced upon APAP-challenge and started recovering by self-renewal at resolution phase without contribution of circulating Ly6Chi monocytes. The latter were recruited in a CCR2 and M-CSF mediated pathway at the necro-inflammatory phase and differentiated into ephemeral Ly6Clo MF subset at resolution phase. Moreover, their inducible ablation resulted in impaired recovery. Microarray based molecular profiling uncovered high similarity between steady state KC and those recovered at the resolution phase. In contrast, KC and monocyte-derived MF displayed distinct pro-restorative genetic signature at the resolution phase. Finally, we show that infiltrating monocytes acquire a pro-restorative polarization manifested by unique expression of pro-angiogenesis mediators and genes involved with inhibition of neutrophil activity and recruitment and promotion of their clearance. Collectively, our results present a novel phenotypic, ontogenic and molecular definition of liver-MF compartment following acute injury. 11 Samples (arrays) were performed. We generated pairwise comparison between all the different macrophages stages, using Partek Genomics Suite. Genes with p?5%[FDR] and a fold-change difference of ?2 or <-2 were selected.
2014-08-01 | E-GEOD-55606 | biostudies-arrayexpress
Project description:Tissue resident macrophages are notoriously heterogeneous, exhibiting discrete phenotypes as a consequence of tissue- and micro-anatomical niche-specific functions, but the molecular basis for this is not understood. We resolved a restricted transcriptional profile for the self-renewing population of peritoneal resident macrophages, which is expressed during homeostasis and inflammation and distinct from other MØ. Prominent within this profile was the expression of Gata6. This study represents a characterisation of the role of Gata6 in peritoneal resident macrophage phenotype. We used microarrays to determine the patterns of gene expression in peritoneal resident MØ in the absence of GATA-6 against wild type.
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Project description:Inflammation is a physiopathological process triggered by infection or tissue damage. Immune system initiates coordinated sequential steps in response to these danger signals. Once the threat has been contained inflammation has to be subsequently shut down. Inflammation resolution is initiated by the reprogramming of pro-inflammatory macrophages toward a pro-resolving profile. This reprogramming is induced in particular by the non-phlogistic engulfment of apoptotic cells, mostly apoptotic neutrophils, a process called efferocytosis. As a matter of fact, macrophages are an essential linchpin regulating both inflammation triggering and sustaining and inflammation resolution. This duality can be achieved through the tremendous plasticity of these innate immune cells. Indeed, depending on microenvironmental signals (cytokines, efferocytosis, growth factors…) macrophages can adopt numerous diverse and sometimes antagonistic phenotypes. The mechanisms governing these transitions remain relatively scattered especially in human. With this project we propose to explore the mechanisms involved in human macrophage reprogramming toward a pro-resolving profile after efferocytosis. The stakes are high due to the estimated prevalence of chronic inflammatory diseases in Western society is 5 to 7%. Chronic inflammation is a burden to patient due to life-long debilitating illness and increased mortality and is also a burden to society due to high costs for therapy and care. Finding new therapies to limit chronic inflammation establishment and persistence is thus a highly valuable goal.
2021-12-01 | E-MTAB-8885 | biostudies-arrayexpress
Project description:We studied the role of Notch2 signaling in Ly6Chi monocyte cell fate during TLR7-induced acute inflammation. To characterize the gene expression changes involved in monocyte differentiation, we subjected monocyte subsets from peripheral blood of wt and myeloid Notch2 mutant mice after Sham or IMQ treatment to RNA-sequencing and gene expression analysis. We found that Cell-intrinsic Notch2 and TLR7-Myd88 pathways independently and synergistically promote Ly6Clo patrolling monocyte development from Ly6Chi monocytes under inflammatory conditions. At the same time TLR7 stimulation in the absence of functional Notch2 signaling promotes resident tissue macrophage gene expression signatures in monocytes and ectopic differentiation of Ly6Chi monocytes into macrophages and dendritic cells. Thus, Notch2 is a master regulator of Ly6Chi monocyte cell fate and inflammation in response to TLR signaling.
2020-08-04 | GSE147492 | GEO
Project description:PPARγ is known for its anti-inflammatory actions in macrophages. However, which macrophage populations express PPARγ in vivo and how it regulates tissue homeostasis in the steady state and during inflammation is not completely understood. We show that lung and spleen macrophages constitutively expressed PPARγ, while other macrophage populations did not. Recruitment of monocytes to sites of inflammation was associated with induction of PPARγ as they differentiated to macrophages. Its absence in these macrophages led to failed resolution of inflammation, characterized by persistent, low-level recruitment of leukocytes. Conversely, PPARγ agonists supported an earlier cessation in leukocyte recruitment during resolution of acute inflammation and likewise suppressed monocyte recruitment to chronically inflamed atherosclerotic vessels. In the steady state, PPARγ deficiency in macrophages had no obvious impact in the spleen but profoundly altered cellular lipid homeostasis in lung macrophages. Reminiscent of pulmonary alveolar proteinosis, LysM-Cre x PPARγflox/flox mice displayed mild leukocytic inflammation in the steady-state lung and succumbed faster to mortality upon infection with S. pneumoniae. Surprisingly, this mortality was not due to overly exuberant inflammation, but instead to impaired bacterial clearance. Thus, in addition to its anti-inflammatory role in promoting resolution of inflammation, PPARγ sustains functionality in lung macrophages and thereby has a pivotal role in supporting pulmonary host defense. The two major subsets of monocytes (Ly-6C+ and Ly-6Clo) from 12-week old C57Bl/6 mice were sorted and the RNA extracted and hybridized to Affymetrix GeneChip® 430 2.0 arrays. We pooled leukocytes from 5 mice for each sort and sorted 3 to 4 separate times for 3 to 4 biological replicates.
2012-10-03 | E-GEOD-32034 | biostudies-arrayexpress
Project description:Dunster2014 - WBC Interactions (Model1)
This is a sub-model of a three-step
inflammatory response modelling study. The model includes distinct
populations of white blood cells namely, macrophages and active and
apoptotic neutrophil populations. Neutrophil apoptosis rate is
predicted to be crucial for the qualitative nature of the
system.
This model is described in the article:
The resolution of
inflammation: a mathematical model of neutrophil and macrophage
interactions.
Dunster JL, Byrne HM, King JR.
Bull. Math. Biol. 2014 Aug; 76(8):
1953-1980
Abstract:
There is growing interest in inflammation due to its
involvement in many diverse medical conditions, including
Alzheimer's disease, cancer, arthritis and asthma. The
traditional view that resolution of inflammation is a passive
process is now being superceded by an alternative hypothesis
whereby its resolution is an active, anti-inflammatory process
that can be manipulated therapeutically. This shift in mindset
has stimulated a resurgence of interest in the biological
mechanisms by which inflammation resolves. The
anti-inflammatory processes central to the resolution of
inflammation revolve around macrophages and are closely related
to pro-inflammatory processes mediated by neutrophils and their
ability to damage healthy tissue. We develop a spatially
averaged model of inflammation centring on its resolution,
accounting for populations of neutrophils and macrophages and
incorporating both pro- and anti-inflammatory processes. Our
ordinary differential equation model exhibits two outcomes that
we relate to healthy and unhealthy states. We use bifurcation
analysis to investigate how variation in the system parameters
affects its outcome. We find that therapeutic manipulation of
the rate of macrophage phagocytosis can aid in resolving
inflammation but success is critically dependent on the rate of
neutrophil apoptosis. Indeed our model predicts that an
effective treatment protocol would take a dual approach,
targeting macrophage phagocytosis alongside neutrophil
apoptosis.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000616.
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To the extent possible under law, all copyright and related or
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2016-08-16 | BIOMD0000000616 | BioModels
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2022-03-24 | GSE188278 | GEO
Project description:Microglia and border-associated macrophages (BAMs) are brain-resident self-renewing cells with important homeostatic functions. However, their fate during and after severe episodes of brain inflammation and their relation to recruited monocyte-derived cells remain poorly understood. Here, we show that Trypanosoma brucei parasites invade the brain via its border regions, triggering a disruption of brain barriers and the recruitment of large numbers of monocytes. Fate-mapping combined with single-cell sequencing revealed the remarkable dynamics of resident macrophages, including microglia accumulation around the ventricular ependyma and an expansion of epiplexus cells. Resident macrophages were important for attracting peripheral immune cells and driving a pro-inflammatory response. However, recruited monocyte-derived macrophages reached higher cell densities and exhibited more transcriptional plasticity, adopting anti-microbial gene expression profiles not observed resident macrophages. Remarkably, recruited macrophages were short-lived and rapidly removed upon disease resolution, while activated resident macrophages progressively reverted towards a homeostatic state. Long-term transcriptional alterations were limited for microglia but more pronounced in BAMs. Together our results reveal the diverging responses and dynamics of resident and recruited macrophages upon Trypanosome invasion of the brain.
2022-08-26 | GSE212078 | GEO