Neutrophils promote M2 polarization of macrophages during Nippostrongylus brasiliensis infection
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Charlie Kim
PROVIDER: E-GEOD-46437 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Microarray profiling of amplified total RNA isolated from neutrophils sorted from naïve, Nippostrongylus brasiliensis (Nb)-infected, or lipopolysaccharide (LPS)-treated mice.
2014-08-30 | GSE46437 | GEO
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/IFNγ 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/IFNγ 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 IL4Rα 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
Project description:We recently reported elimination of renal crystals and migration of macrophages (MM-OM-^F) around crystals in hyperoxaluric mice, suggesting MM-OM-^Fs might eliminate crystals. MM-OM-^Fs are of 2 phenotypes: inflammatory (M1) and anti-inflammatory (M2). Because M2MM-OM-^Fs are considered to be involved in tissue repair and regeneration, we focused attention on their suppressive role in renal crystal formation. Hence, we investigated the gene array profiling of renal macrophages in stone model mice and CSF-1-deficient stone model mice. B6C3Fe a/a-Csf1op/J wild type/homozygous mice were admistered 80mg/kg gyyoxylate (GOX) for 6days, then the kidneys were extracted and sorted CD11b+/CD11c+ macrophages using autoMACS. The gene expression of WT- and op/op-macrophages were investigated using bone marrow derived M1/M2 macrophages as controls.
2013-10-22 | E-GEOD-51466 | biostudies-arrayexpress
Project description:A gastrointestinal nematode parasite of rats.
| PRJNA20447 | ENA
Project description:A gastrointestinal nematode parasite of rats.
| PRJNA20449 | ENA
Project description:A gastrointestinal nematode parasite of rats.
| PRJNA20445 | ENA
Project description:Alveolar macrophages from Cx3cR1-CreER x Rosa26-tandem dimer Tomato(TdT) control and infected mice were sort-purified on live CD45+CD64+F4/80+CD11c+SiglecF+ and then sorted based on expression of TdT, with tissue-resident cells being TdT- and monocyte-derived cells TdT+. Illumina-compatible libraries were generated using the NEBNext Ultra II DNA Library Prep Kit for Illumina (catalog no. E7645S; New England BioLabs) and sequenced using an Illumina NextSeq 550 in a single-end 75-base pair (bp) read configuration. Bulk RNA-seq analysis was performed in accordance with the nf-core RNA-seq guidelines v.1.4.2. The output reads were aligned to the GRCm38 genome using STAR, followed by gene count generation using featureCounts and StringTie. Read counts were normalized and compared for differential gene expression using DESeq2 with significance at a false discovery rate-adjusted P<0.05. We report that at day 7 monocyte-derived alveolar macrophages had a gene expression profile distinct from tissue-derived alveolar macrophages while by day 14 the monocyte-derived macrophages had assumed gene expression profiles more similar to tissue-derived alveolar macrophages, as determine by pairwise Euclidean distance calculation and principal components analysis.
2022-01-13 | GSE189675 | GEO
Project description:Microarray profiling of amplified total splenic RNA isolated from TLR9-, TLR7-, UNC93b1- or MYD88- deficient mice or their C57BL/6 controls 24h after mock infection or infection with Plasmodium chabaudi. 4 independent replicates collected from each genotype/infection group, RNA isolated and amplified from whole spleen. Hybridized as a one color experiment.
2013-09-21 | E-GEOD-41496 | biostudies-arrayexpress
Project description:Animal-parasitic nematodes have thus far been largely refractory to genetic manipulation, and methods employed to effect RNA interference (RNAi) have been ineffective or inconsistent in most cases. We describe here a new approach for genetic manipulation of Nippostrongylus brasiliensis, a widely used laboratory model of gastrointestinal nematode infection. N. brasiliensis was successfully transduced with Vesicular Stomatitis Virus glycoprotein G (VSV-G)-pseudotyped lentivirus. The virus was taken up via the nematode intestine, RNA reverse transcribed into proviral DNA, and transgene transcripts produced stably in infective larvae, which resulted in expression of the reporter protein mCherry. Improved transgene expression was achieved by incorporating the C. elegans hlh11 promoter and the tbb2 3´-UTR into viral constructs. MicroRNA-adapted short hairpin RNAs delivered in this manner were processed correctly and resulted in partial knockdown of β-tubulin isotype-1 (tbb-iso-1) and secreted acetylcholinesterase B (ache-B). The system was further refined by lentiviral delivery of double stranded RNAs, which acted as a trigger for RNAi following processing and generation of 22G-RNAs. Virus-encoded sequences were detectable in F1 eggs and third stage larvae, demonstrating that proviral DNA entered the germline and was heritable. Lentiviral transduction thus provides a new means for genetic manipulation of parasitic nematodes, including gene silencing and expression of exogenous genes.
| S-EPMC7864396 | biostudies-literature
Project description:Infections with helminth parasites are endemic in the developing world and are a target for intervention with new therapies. Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic effects in inflammation and immune responses. We investigated the role of MIF in a naturally cleared model of helminth infection in rodents, Nippostrongylus brasiliensis. At day 7 postinfection, MIF-deficient (MIF-/-) mice had reduced parasite burden and mounted an enhanced type 2 immune response (Th2), including increased Gata3 expression and interleukin-13 (IL-13) production in the mesenteric lymph nodes (MLNs). Bone marrow reconstitution demonstrated that MIF produced from hematopoietic cells was crucial and Rag1-/- reconstitution provided direct evidence that MIF-/- CD4+ T cells were responsible for the augmented parasite clearance. MIF-/- CD4+ T cells produced less IL-6 postinfection, which correlated with enhanced Th2 responses. MIF-/- CD4+ T cells exhibited lower nuclear factor-κB activation, potentially explaining the reduction in IL-6. Finally, we demonstrated enhanced clearance of the parasite and Th2 response in wild-type mice treated with the MIF tautomerase inhibitor, sulforaphane, a compound found naturally found in cruciferous vegetables. These results are the first to describe the importance of the tautomerase enzyme activity in MIF function in N. brasiliensis infection.
| S-EPMC5053838 | biostudies-literature