Expression in IFN-gamma treated control and Atg5-/- macrophages
Ontology highlight
ABSTRACT: Type-I (α/β) and -II (γ) interferons (IFN), through an incompletely understood combination of redundant and unique mechanisms, are essential for host resistance to viral infection. We report a requirement for the Atg5-Atg12/Atg16L1 autophagosome elongation complex in IFNγ-mediated control of murine norovirus in macrophages. We use microarrays to compare transcriptional changes induced in control and Atg5 deficient macrophages by IFNγ treatment. Bone marrow derived macrophages were generated from Atg5flox/flox and Atg5flox/flox+LysM cre mice and treated with media alone or 100U/ml of IFNγ for 14 hrs. RNA was extracted using Trizol (Invitrogen) and 10 µg of RNA hybridized to Affymetrix microarrays.
Project description:Type-I (α/β) and -II (γ) interferons (IFN), through an incompletely understood combination of redundant and unique mechanisms, are essential for host resistance to viral infection. We report a requirement for the Atg5-Atg12/Atg16L1 autophagosome elongation complex in IFNγ-mediated control of murine norovirus in macrophages. We use microarrays to compare transcriptional changes induced in control and Atg5 deficient macrophages by IFNγ treatment.
Project description:The goal of this study is to compare the transcriptome profiling (RNA-seq) of two CD25 regulatory T cell subsets isolated from secondary lymphoid organs of mice lacking autophagy in their dendritic cells. CD25High and CD25Low regulatory T cells were isolated from Atg5 flox/flox CD11c Cre +/- (Atg5 -/- DC) mice and their littermate controls, Atg5 flox/flox CD11c Cre -/- (Atg5 +/+ DC), under steady state conditions.
Project description:Saccharomyces cerevisiae ATG5, Conserved protein involved in autophagy and the Cvt pathway; undergoes conjugation with Atg12p to form a complex involved in Atg8p lipidation; Atg5p-Atg12p conjugate enhances E2 activity of Atg3 by rearranging its catalytic site, also forms a complex with Atg16p; the Atg5-Atg12/Atg16 complex binds to membranes and is essential for autophagosome formation; also involved in methionine restriction extension of chronological lifespan in an autophagy-dependent manner [Source:SGD;Acc:S000006070], is differentially expressed in 1 experiment(s);
Project description:Saccharomyces cerevisiae ATG5, Conserved protein involved in autophagy and the Cvt pathway; undergoes conjugation with Atg12p to form a complex involved in Atg8p lipidation; Atg5p-Atg12p conjugate enhances E2 activity of Atg3 by rearranging its catalytic site, also forms a complex with Atg16p; the Atg5-Atg12/Atg16 complex binds to membranes and is essential for autophagosome formation; also involved in methionine restriction extension of chronological lifespan in an autophagy-dependent manner [Source:SGD;Acc:S000006070], is expressed in 1 baseline experiment(s);
Project description:Susceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci. One Crohn's disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 (ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment. ATG16L1- and ATG5-deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1-deficient Paneth cells including increased expression of genes involved in peroxisome proliferator-activated receptor (PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy-protein-deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells. Experiment Overall Design: 4 Samples: 2 replicates of Atg16-hypomorph Paneth cells and 2 replicates of Wildtype Paneth cells.
Project description:Mycobacterium tuberculosis impairs host lysosomal trafficking pathways. Xenophagy and LC3-associated phagocytosis (LAP) are lysosomal trafficking pathways that normally clear intracellular microbes. The xenophagy and LAP pathways depend upon ATG5 and ATG7, which result in the lipidation of LC3-I to LC3-II. How Mtb undermines these innate immune defenses of the host in not well understood. We used a transposon sequencing (Tn-seq) screen to identify bacterial factors that are required for the bacilli to resist ATG5 and ATG7-dependent processes. We found that that mutants defective in production of PDIM are attenuated in murine macrophages, and they are able to survive in macrophages lacking ATG5 or ATG7.
Project description:Depletion of autophagy-associated protein 5 (Atg5), specifically within the eosinophil lineage in mice, resulted in increased body weight, impaired glucose metabolism, and structural alterations in adipose tissue. Our findings highlight that Atg5 influences the functional activity of eosinophils within adipose tissue rather than their quantity. To gain a deeper understanding of the molecular mechanisms underlying ATG5's role in eosinophils, we conducted total RNA-seq analyses on control and Atg5-deficient eosinophils isolated from both bone marrow and blood of mice.
Project description:The goal of this experiment was to validate a classification model built on other bulk transcriptomic data that was capable of identifying in vitro stimulated M-CSF differentiated macrophages. Specifically, the classification model was capable of distinguishing: M-LPSearly (2-4 hours) M-LPSlate (18-24 hours) M-LPS+IFNγ M-IFNγ M-IL4 M-IL-10 M-dex
Project description:Danio rerio atg5, ATG5 autophagy related 5 homolog (S. cerevisiae) [Source:ZFIN;Acc:ZDB-GENE-040801-149], is expressed in 1 baseline experiment(s);