Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Natural killer cells regulate pulmonary macrophages polarization in host defense chlamydial lung infection

ABSTRACT: NK cells and pulmonary macrophages both are important components of innate immunity. The interaction between NK cells and pulmonary macrophages during Chlamydia muridarum（C. muridarum）respiratory infections is poorly understood. In this study, we explored the effect of NK cells on regulation of pulmonary macrophage function during chlamydial lung infection. We found that NK depletion led to polarization of pulmonary macrophages from M1 to M2 phenotype, and this related to significantly reduced miR-155 expression in pulmonary macrophage. Using adoptive transfer approach, we found that the recipient mice receiving lung macrophages isolated from C. muridarum-infected NK-cell-depleted mice exhibited an increased bacterial load and severe inflammation in the lung upon chlamydial challenge when compared with the recipients of lung macrophages from infected IgG -treated mice. Herein, the effects of NK cells on macrophage polarization were examined in vitro. We found that NK cells from chlamydial-infected mice (iNK) significantly induced M1 polarization compared to that from sham-infected mice (uNK). Inhibition of miR-155 expression in macrophages attenuated M1 polarization induced by iNK, while miR-155 over-expression enhanced it. Furthermore, neutralization of IFN-γ in the coculture system decreased the expression of miR-155 by macrophages, and resulted in diminished M1 polarization induced by iNK cells. The data indicates that NK cells direct M1 polarization through up-regulation of miR-155 by IFN-γ production, and NK-regulated macrophage polarization is functionally relevant to host defense against chlamydial infection.

ORGANISM(S): synthetic construct Mus musculus

PROVIDER: GSE183577 | GEO | 2022/01/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Control of the inflammatory macrophage transcriptional signature by miR-155

Project description:Classically activated (M1) macrophages protect from infection but can cause inflammatory disease and tissue damage while alternatively activated (M2) macrophages reduce inflammation and promote tissue repair. Modulation of macrophage phenotype may be therapeutically beneficial and requires further understanding of the molecular programs that control macrophage differentiation. A potential mechanism by which macrophages differentiate may be through microRNA (miRNA), which bind to messenger RNA and post-transcriptionally modify gene expression, cell phenotype and function. The inflammation-associated miRNA, miR-155, was rapidly up-regulated over 100-fold in M1, but not M2, macrophages. Inflammatory M1 genes and proteins iNOS, IL-1b and TNF-a were reduced up to 72% in miR-155 knockout mouse macrophages, but miR-155 deficiency did not affect expression of genes associated with M2 macrophages (e.g., Arginase-1). Additionally, a miR-155 oligonucleotide inhibitor efficiently suppressed iNOS and TNF-a gene expression in wild-type M1 macrophages. Comparative transcriptional profiling of unactivated (M0) and M1 macrophages derived from wild-type and miR-155 knockout (KO) mice revealed an M1 signature of approximately 1300 genes, half of which were dependent on miR-155. Real-Time PCR of independent datasets validated miR-155's contribution to induction of iNOS, IL-1b, TNF-a, IL-6 and IL-12, as well as suppression of miR-155 targets Inpp5d, Tspan14, Ptprj and Mafb. Overall, these data indicate that miR-155 plays an essential role in driving the differentiation and effector potential of inflammatory M1 macrophages. Total RNA was prepared from bone marrow-derived macrophages of miR-155 knockout mice (n=2 independent mice) treated in M0, M1 or M2 conditions (n=2 replicates per condition originating from different mice)

2016-07-15 | E-GEOD-77425 | biostudies-arrayexpress

Control of the inflammatory macrophage transcriptional signature by miR-155

2016-07-15 | GSE77425 | GEO

Anti-tumor Effect and Action Mechanism of Exosomes Derived from Toxoplasma gondii-Infected Dendritic Cells in Mice Colorectal Cancer

Project description:Toxoplasma gondii is an obligate intracellular protozoan with anti-tumor activity against a variety of cancers. However, the therapeutic effect of T. gondii on colorectal cancer is unclear, and using direct Toxoplasma infection in immunotherapy involves safety concerns. This study investigated the anti-tumor effect and mechanism of exosomes derived from dendritic cells (DC) infected with T. gondii (Me49-DC-Exo). We used the density gradient centrifugation to isolate exosomes from uninfected DCs (DC-Exo) and T. gondii Me49-infected DCs (Me49-DC-Exo). The isolated exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Me49-DC-Exo significantly inhibited tumor growth and reduced the proportion of M2 macrophages in the blood of tumor-bearing mice. In vitro, Me49-DC-Exo suppressed macrophage (RAW264.7) polarization to M2 phenotype. miRNA sequencing revealed that multiple miRNAs in Me49-DC-Exo were differentially expressed compared with DC-Exo. miR-182-5p, miR-155-5p, miR-125b-2-3p, and miR-155-3p were up-regulated, while miR-9-5p was significantly down-regulated. Transfecting mimics or inhibitors of these differential miRNAs into RAW264.7 cells showed that miR-155-5p promoted M1 macrophage polarization while inhibiting M2 macrophage polarization. Bioinformatics prediction and dual-luciferase reporter assay confirmed the suppressor of cytokine signaling 1 (SOCS1) as a direct target of miR-155-5p. Silencing SOCS1 gene expression in RAW264.7 cells increased CD86 + CD206 - M1 macrophage proportion and inducible nitric oxide synthase and tumor necrosis factor-α mRNA levels. However, arginase1 and transglutaminase 2 expression levels decreased. These results suggest that the exosomes inhibit macrophage polarization to M2 phenotype and regulate SOCS1 expression by delivering functional miR-155-5p. These findings provide new ideas for colorectal cancer immunotherapy.

2022-02-24 | GSE197114 | GEO

Unraveling the mechanism of ethyl acetate extract from Prismatomeris connata Y. Z. Ruan root in treating pulmonary fibrosis: insights from bioinformatics, network pharmacology, and experimental validation

Project description:Pulmonary fibrosis (PF) is a terminal lung disease characterized by fibroblast proliferation, accumulation of extracellular matrix accumulation, inflammatory damage, and tissue structure destruction. The pathogenesis of this disease, especiallyparticularly idiopathic pulmonary fibrosis (IPF), is still remains unknown. Macrophages play a significant rolemajor roles in organ fibrosis diseases, including pulmonary fibrosis. The phenotype and polarization of macrophages are closely associated with the process of pulmonary fibrosis. A new direction in drug research on for antipulmonary fibrosis is focuseds on developing drugs that maintain the stability of the pulmonary microenvironment. Here, tThrough bioinformatics analysis and experiments involving bleomycininduced pulmonary fibrosis in mice, we confirmed the importance of macrophage polarization in IPF. The analysis revealed that macrophage polarization in IPF involves a change in the phenotypice spectrum. Furthermore, the experiments demonstrated showed high expression of M2-type macrophage-related-associated biomarkers and inducible nitric oxide synthase, thus indicating an imbalance in M1/M2 polarization of pulmonary macrophages in mice with pulmonary fibrosis. Our investigation revealed that the ethyl acetate extract (HG2) obtained from the roots of Prismatomeris connataPrismatomeris connata Y. Z. Ruan exhibits therapeutic efficacy against bleomycin-induced pulmonary fibrosis. HG2 demonstrates the ability to modulates macrophage polarization, alterations in the TGF‐β/Smads pSmad pathway, and downstream protein expression in the context of pulmonary fibrosis. Drawing upon On the basis of our findings, we believe that HG2 exhibits has potential as a novel component of traditional Chinese medicine component for treating pulmonary fibrosis.

2024-01-07 | PXD048007 | Pride

Next Generation Sequencing Analysis of Healthy donors and rhumatoid arthritis patients with or without anti-TNF-treatment

Project description:Introduction: We previously reported a specific defect of rheumatoid arthritis (RA) monocyte polarization to anti-inflammatory M2-like macrophages related to increased miR-155 expression in all RA patients except those receiving adalimumab (ADA). In this longitudinal study, we examined whether different tumor necrosis factor inhibitors were able to restore monocyte polarization to M2-like macrophages and their effect on the transcriptomic signature. Methods: M2-like polarization induced by human serum AB was studied in 7 healthy donors and 20 RA patients included in the ABIRA cohort before and 3 months after starting ADA or etanercept (ETA). The differential gene expression of M2- and M1-related transcripts was studied in macrophage-derived monocytes after differentiation. Results: At baseline, RA monocytes showed a defect of polarization to M2-like macrophages as compared with healthy donor monocytes, which was negatively correlated with disease activity. M2-like polarization from circulating monocytes was restored only with ADA and not ETA treatment. The transcriptomic signature demonstrated downregulation of M2-related transcripts and upregulation of M1-related transcripts in active RA. In patients receiving ADA, the transcriptomic signature of M2- related transcripts was restored. Conclusion: This longitudinal study demonstrates that ADA but not ETA is able to restore the M2-like polarization of monocytes that is defective in RA

2022-02-16 | GSE196743 | GEO

polyA+ RNA sequencing on FACS sorted alveolar macrophages (CD45+SiglecF+CD11c+) from air and cigarette-smoke exposed wild type and miR-155 KO mice

Project description:Chronic obstructive pulmonary disease (COPD) is a highly prevalent respiratory disease characterized by airflow limitation and chronic inflammation. MiR-155 is described as an ancient regulator of the immune system. Our objective was to establish a role for miR-155 in cigarette smoke (CS)-induced inflammation and COPD. We demonstrate increased miR-155 expression by RT-qPCR in lung tissue of smokers without airflow limitation and patients with COPD compared to never smokers and in lung tissue and alveolar macrophages of CS-exposed mice compared to air-exposed mice. In addition, we exposed wild type and miR-155 deficient mice to CS and show an attenuated inflammatory profile in the latter. Alveolar macrophages were sorted by FACS from the different experimental groups and their gene expression profile was analyzed by RNA sequencing. This analysis revealed increased expression of miR-155 targets (including the NF-κB inhibitor rassf6) and an attenuation of the CS-induced increase in inflammation-related genes in miR-155 deficient mice. Finally, intranasal instillation of a specific miR-155 inhibitor significantly attenuated the CS-induced pulmonary inflammation in mice. In conclusion, we highlight a role for miR-155 in CS-induced inflammation and the pathogenesis of COPD, implicating miR-155 as a new therapeutic target in COPD.

2019-12-16 | GSE137653 | GEO

Natural killer cells regulate pulmonary macrophages polarization in host defense chlamydial lung infection

Project description:Natural killer cells regulate pulmonary macrophages polarization in host defense chlamydial lung infection

| PRJNA761349 | ENA

MiR expression profiles in M1-polarized compared with unstimulated (MÐ¤) bone marrow-derived macrophage cells

Project description:The global change of the miR expression profile during atherosclerosis is due to the infiltration of different types of leukocytes into the arterial vessel wall in addition to disease-specific regulation in vascular cells. Monocyte-derived macrophage accumulation in the subintimal region is critical in the formation of atherosclerotic plaques. It is currently unknown which miRs are involved in the atherogenic macrophage response. The comparison of the miR expression profile in LPS/Interferon-gamma activated mouse macrophages with the miR expression in the unstimulated mouse macrophages was performed to detect M1-type macrophage-enriched miRs. This screening combined with our miR profiling in atherosclerotic vessels may help to identify M1-type macrophage-enriched miRs in atherosclerotic vessels that may play a role in the macrophage function during atherogenesis. Bone marrow cells were harvested from femura of 6- to 8-week-old female C57BL/6 mice, re-suspended in DMEM-F12/10% FCS/10% L929-conditioned medium, and cultured for 7 days to differentiate into primary macrophages. F4/80 and CD11b expression was determined by flow cytometry to confirm the macrophage phenotype. Macrophages were stimulated with LPS (100ng/ml, 14 hours) and INF-g (10ng/ml, 6 hours), and the M1 polarization was verified by quantification of mannose receptor C type 1 (MRC1), arginase II (ArgII), inducible nitric oxide synthase (iNOS), and arginase I (ArgI) by qRT-PCR. Total RNA (M1-type and unstimulated (MÐ¤) macrophages) was isolated using the mirVana microRNA Isolation Kit.

2012-12-26 | E-GEOD-33453 | biostudies-arrayexpress

Expression data from macrophage maturation and polarization c-Myc in alternative macrophage activation experiments

Project description:In response to microenvironmental signals macrophages undergo different activation, indicated as classic/M1 and alternative/M2 polarization. C-Myc transcription factor could be an essential player in M2 polarization. Functional relevance of c-Myc in M2 macrophage biology is investigated by evaluating the effect of 100-58F4, on the transcriptional profile induced on human macrophages by IL-4. Human monocytes were obtained from normal donor buffy coats by two-step gradient centrifugation using Ficoll (Biochrom) and Percoll (Amersham). Non-adherent cells were discarded, and the purified monocytes were incubated for 7 days in RPMI 1640 (Biochom) supplemented with 10% FCS (HyClone) and 100 ng/mL M-CSF to obtain resting macrophages. Macrophage polarization was obtained by removing the culture medium and culturing cells in RPMI 1640 supplemented with 10% FCS and 100 ng/mL LPS plus 20 ng/mL IFN-gamma (M1 polarization) or 20 ng/mL IL-4 (M2 polarization) for 24 h. When needed, chemical inhibitors were added with IL-4.

2011-09-15 | E-GEOD-32164 | biostudies-arrayexpress

Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages

Project description:The proteasome is a central regulatory hub for intracellular signaling by degrading numerous signaling mediators. Immunoproteasomes are specialized types of proteasomes known to be involved in shaping adaptive immune responses, but their role for innate immune signaling is elusive. Here, we analyzed immunoproteasome function for polarization of alveolar macrophages which are highly specialized tissue macrophages of the alveolar surface of the lung. Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNÎ³ transcriptionally induced all three immunoproteasome subunits LMP2, LMP7, and MECL-1. In contrast, IL-4 triggered alternative (M2) activation was accompanied by posttranscriptional upregulation of LMP2 and LMP7. Accordingly, immunoproteasome activity increased in M1 cells, and to some extent under M2 conditions. Analyzing the polarization capability from LMP7 deficient mice revealed no effect on the LPS/IFNÎ³ triggered M1 profile, but uncovered a distorted M2 profile for IL-4 stimulated LMP7-/- alveolar macrophages as characterized by increased M2 marker gene expression and CCL17 cytokine release. This shift in immunoproteasome-dependent M2 polarization was accompanied by amplified AKT/STAT6 activation and IRF4 expression in LMP7-/- alveolar macrophages. IL-13 stimulation of LMP7 deficient cells induced a similar M2 skewed profile and IL4RÎ± protein expression was generally elevated in LMP7-/- alveolar macrophages, indicating that amplified IL4R signaling in immunoproteasome defective cells may contribute to augmented M2 polarization. Importantly, treatment with an LMP7-specific proteasome inhibitor recapitulated the findings of genetic LMP7 inactivation. Our results thus suggest a novel role of immunoproteasome function for regulating innate immune function of macrophages by limiting IL4R expression and signaling. Expression data of M0 and M2 macrophages derived from Lmp7 k.o. and control animals

2016-06-29 | E-GEOD-72000 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data