Antiviral function of type I and type III interferons in the olfactory epithelium
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PROVIDER: PRJNA645461 | ENA |
REPOSITORIES: ENA
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Project description:Background: The olfactory epithelium (OE) is one of the few sites where environmental pathogens can gain direct access to the brain. Despite this vulnerable arrangement, little is known about the protective mechanisms in the OE to prevent viral infection and subsequent entry into the brain. Methods: We systematically investigated acute responses in the olfactory mucosa (OM) upon exposure to vesicular stomatitis virus (VSV) by RNA-seq. VSVs were nasally inoculated into C57BL/6 mice. OM were dissected for gene expression analysis at different time points after viral inoculation. Interferon functions were determined by comparing viral gene expression in interferon (Ifn) receptor knockout (Ifnar1-/- and Ifnlr1-/-) with wildtype OM. Results: Antiviral responses were observed as early as 24hrs post viral exposure in the OM. Amongst the rapidly upregulated transcripts observed were specific type I as well as type III Ifns and interferon stimulated genes. Genetic analyses demonstrated that both type I and type III IFN signaling are required for the suppression of viral replication in the OM. Nasal IFNb1 or IFNl2 administration effectively reduces viral load in the OM. Conclusions: OE possesses innate ability to respond and suppress viral infection. Type I and type III IFNs actively participate in the OE’s antiviral functions. Nasal IFN application effectively blocks viral replication in the OE suggesting therapeutic potential against viral insult.
2023-07-03 | GSE154235 | GEO
Project description:Type I and III interferons (IFNs) are critical antiviral molecules thought to activate similar signaling cascades resulting in the induction of shared downstream IFN-stimulated genes. This study reveals an unappreciated fundamental difference in the signal transduction downstream of type I and type III IFNs that has broad implications for their functionalities during infection and inflammation.
2019-09-30 | GSE115198 | GEO
Project description:Administration of recombinant interferons to 3D brain organoid cultures infected with HSV reveals a strong antiviral effect of IFN-alpha against HSV
2021-04-09 | GSE145496 | GEO
Project description:Type-I-Interferons induce the decimation of antiviral B cells at the onset of chronic infection
| PRJNA327851 | ENA
Project description:Tissue damage and repair are hallmarks of inflammation. Despite a wealth of information on the mechanisms that govern tissue damage, mechanistic insight on how inflammation affects repair is lacking. Here, we investigated how interferons influence tissue repair after damage to the intestinal mucosa. We found that type III, not type I or II, interferons delay epithelial cell regeneration by inducing the upregulation of Z-DNA-binding protein 1 (ZBP1). Z-nucleic acids formed following intestinal damage are sensed by ZBP1, leading to Caspase-8 activation, and cleavage of Gasdermin C (GSDMC). Cleaved GSDMC drives epithelial cell death by pyroptosis and delays repair of the large or small intestine after colitis or irradiation, respectively. The type III interferon/ZBP1/Caspase-8/GSDMC axis is also active in patients with inflammatory bowel disease (IBD). Our findings highlight the capacity of type III interferons to delay gut repair, which has important implications for IBD patients or individuals exposed to radiation therapies.
2024-11-01 | GSE277150 | GEO
Project description:Tissue damage and repair are hallmarks of the inflammatory process. Despite a wealth of information on the mechanisms that govern tissue damage, mechanistic insight on how inflammatory mediators affect repair is lacking. Here, we investigated how interferons influence tissue repair after damage to the intestinal mucosa driven by inflammation or genotoxicity. We found that type III, but not type I or II, interferons delay epithelial cell regeneration by inducing the upregulation of Z-DNA-binding protein 1 (ZBP1). Z-nucleic acids formed during the damage and repair process are then sensed by ZBP-1, leading to Caspase-8 activation, and cleavage of Gasdermin C (GSDMC). Cleaved GSDMC drives epithelial cell death by pyroptosis and delays the re-epithelialization of the large or small intestine after colitis or irradiation, respectively. We also found that the type III interferon/ZBP1/Caspase-8/GSDMC pathway is activated in patients with inflammatory bowel disease (IBD). Our findings highlight a molecular signaling cascade initiated by type III interferons that delays intestinal tissue repair, which has important implications for IBD patients or individuals exposed to radiation therapies.
2024-11-01 | GSE276837 | GEO
Project description:The lineage of wild-type horizontal basal cells (HBC) stem cells from the olfactory epithelium were profiled by single-cell RNA-Seq (10X v3 chemistry) to identify differences in aged versus not-aged adult stem cells mRNA expression profiles
2020-11-16 | GSE157100 | GEO
Project description:Mouse Olfactory Epithelium, whole olfactory mucosa, mouse
| PRJNA660060 | ENA
Project description:Olfactory sensory neurons (OSNs) expressing the same olfactory receptor (OR) are randomlydispersed within the same olfactory epithelial zone. To date, between 4 and 12 zones havebeen defined based on OR expression by in-situ hybridization studies. However, the totalnumber of zones, their organisation, molecular identity, and their distribution across thedorsal-ventral, anterior-posterior and lateral-medial axes are still unknown. To address thesequestions we propose to perform RNA-seq on sequential cryosections along the dorsalventraland anterior-posterior axes. This will provide a spatial dimension to the quantitativedata we already have on the number of each neuron type in the entire epithelium. We aim touse this as preliminary data for a grant application to completely resolve the 3D organisationof the olfactory epithelium at a cellular level. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2016-02-09 | E-ERAD-433 | biostudies-arrayexpress