Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neutrophil S100A9 supports M2 macrophage niche formation in granulomas

ABSTRACT: Mycobacterium infection gives rise to granulomas predominantly composed of inflammatory M1-like macrophages, with bacteria-permissive M2 macrophages also detected in deep granulomas. Our histological analysis of Mycobacterium bovis bacillus Calmette-Guerin-elicited granulomas in guinea pigs revealed that S100A9-expressing neutrophils bordered a unique M2 niche within the inner circle of concentrically multilayered granulomas. We evaluated the effect of S100A9 on macrophage M2 polarization based on guinea pig studies. S100A9-deficient mouse neutrophils abrogated M2 polarization, which was critically dependent on COX-2 signaling in neutrophils. Mechanistic evidence suggested that nuclear S100A9 interacts with C/EBPβ, which cooperatively activates the Cox-2 promoter and amplifies prostaglandin E2 production, followed by M2 polarization in proximal macrophages. Since the M2 populations in guinea pig granulomas were abolished via treatment with celecoxib, a selective COX-2 inhibitor, we propose the S100A9/Cox-2 axis as a major pathway driving M2 niche formation in granulomas.

ORGANISM(S): Mus musculus

PROVIDER: GSE162991 | GEO | 2023/03/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Distinct population of immune suppressive macrophages differentiate from monocytic myeloid-derived suppressor cells in cancer

Project description:Here, we report that functional heterogeneity of macrophages in cancer could be determined by the nature of their precursors: monocytes (Mon) and monocytic myeloid-derived suppressor cells (M-MDSC). Macrophages differentiated from M-MDSC, but not from Mon were immune suppressive with genomic profile matching that of M-MDSC. Immune suppressive activity of M-MDSC derived macrophages was dependent on the persistent expression of S100A9 protein in these cells. S100A9 also promoted M2 polarization of macrophages. Tissue resident and Mon derived macrophages lacked expression of this protein. S100A9 dependent immune suppressive activity of macrophage was mediated via transcription factor CEBP/β. The presence of S100A9 positive macrophages in tumor tissues was associated with shorter survival in patients with head and neck cancer and poor response to PD-1 antibody treatment in patients with metastatic melanoma. Thus, this study revealed the pathway of the development of immune suppressive macrophages and suggested approach to their selective targeting.

2020-12-14 | GSE162353 | GEO

Mus musculus

Project description:Neutrophils promote M2 polarization of macrophages during Nippostrongylus brasiliensis infection

| PRJNA200342 | ENA

Development of oligonucleotide microarray to study global gene expression profile in guinea pigs in response to tuberculosis infection

Project description:In this study we developed a guinea pig oligonucleotide microarray (GPOM) comprising of a total number of 45,220 features including 43,803 valid features from different mammalian species. These features are inclusive of 2971 newly annotated probes corresponding to 344 unique genes of guinea pig. As a case study, we utilized this array to examine the gene expression profile in guinea pig lungs in response to infection with Mycobacterium tuberculosis. Studying the global gene expression profile in guinea pigs allowed identification of the disease signature of pulmonary TB infection represented by several unique genes that are differentially regulated in this model. While, 1344 unique genes exhibited marked up regulation, 1856 genes were significantly down regulated. The newly developed tool not only finds its utility in studying the global gene expression profile associated with vaccination and/or M. tuberculosis infection in this highly useful animal model but would also be immensely useful in identification of new drug targets, testing of therapies, molecular genetic analysis for diseases other than tuberculosis as well. Genotypic Technology designed Custom Cavia porcellus 4x44k Gene Expression Array (Agilent-AMADID-019424) * In order to validate the GPOM developed in this study, we compared the gene expression profile of guinea pig lungs at 10 weeks post- M. tuberculosis infection with respect to that obtained from normal uninfected animals. To address this, guinea pigs were aerosol infected with M. tuberculosis, lungs were harvested at 10 weeks post-infection and RNA obtained from infected lungs was employed for cDNA synthesis and microarray hybridization. The gene expression was compared with the RNA sample obtained from the lungs of normal uninfected guinea pigs.

2012-10-01 | E-GEOD-32447 | 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

Gene expression profling of Mycobacterium tuberculosis H37Rv and H37RvΔdosSΔdosT in 0.2% glucose/acetate under aerobic/hypoxic conditions

Project description:The present study reports the gene expression data of Mycobacterium tuberculosis H37Rv and H37RvΔdosSΔdosT (DKO) grown on 0.2 % acetate/glucose under aerobic/hypoxic conditions. Acetate was reported to be present in granulomas of Mycobacterium tuberculosis infected guinea pigs which are also hypoxic. By exposing Mycobacterium tuberculosis H37Rv and H37RvΔdosSΔdosT to different combinations of granulomatous stresses (acetate/glucose and aerobic/hypoxic conditions) alongwith other experimental data, we were able to delineate a new signaling pathway that activates DevR (DosR) regulon through Acetyl phosphate. The presence of two pathways highlights the importance of targeting DevR and not DevS/DosT for intercepting DevRST signalling cascade.

2019-01-01 | GSE117428 | GEO

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

Development of oligonucleotide microarray to study global gene expression profile in guinea pigs in response to tuberculosis infection

2012-10-01 | GSE32447 | GEO

RNAseq profiling of FACS-sorted zebrafish larval macrophages reveals similarities with human M1 and M2 transcriptome signatures

Project description:We used different zebrafish transgenic lines to sort macrophages, neutrophils and immature lymphoid cells from 5-6 day old zebrafish larvae and analyzed their transcriptomes. Comparison between the different transcriptomes and gene ontology analysis revealed specificities for each cell population. Comparison with previously published data showed that zebrafish larval macrophages expressed several known human M1 and M2 macrophages. Transcriptome analysis of uninfected and infected macrophages from embryos infected by of Mycobacterium marinum revealed infection induced transcriptional changes and a shift towards M1 transcriptomic signature.

2017-08-11 | GSE78954 | GEO

RNAseq profiling of zebrafish larval macrophages reveals similarities with human M1 and M2 transcriptome signatures

2018-12-11 | GSE68920 | GEO

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

2011-09-16 | GSE32164 | GEO