Dataset Information

Effect of depletion of Med23 on gene expression during VSV infection of MEF and BMDM cells.

ABSTRACT: The detection of cytosolic viral nucleic acids via pattern recognition receptors (PRRs) activates multiple signaling pathways, leading to the production of interferons (IFNs), which are essential for host survival during viral infection. Precise control of PRR gene expression is crucial for maintaining immune homeostasis. Here, we showed that Mediator complex subunit 23 (Med23) is required for the precise production of the innate immune receptor RIG-I in response to RNA virus infection. Med23 deficiency markedly enhances the production of type I IFNs, proinflammatory cytokines and IFN-stimulated genes (ISGs) in both multiple cell lines and primary macrophages infected with RNA viruses or stimulated with poly(I:C). Myeloid-specific Med23 knockout mice were generated to test the critical role of Med23 in host resistance to RNA virus infection in vivo. Mechanistically, Med23 interacts with the transcription factor forkhead box O3 (Foxo3) to negatively regulate RIG-I, thereby modulating IFN-I signaling. Collectively, these findings elucidate a previously unrecognized role of Med23 as a gatekeeper of the RIG-I-mediated antiviral innate immune response and suggest a potential target for controlling viral infection.

ORGANISM(S): Mus musculus

PROVIDER: GSE281340 | GEO | 2025/06/26

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Although mast cells elicit proinflammatory and type I IFN responses upon VSV infection, in response to L.monocytogenes (L.m) or S. Typhimurium (S.t), such cells elicit a transcriptional program devoid of type I IFN response. Balanced induction of proinflamatory and type I interferon (IFN) responses upon activation of Toll like receptors (TLRs) determines the outcome of microbial infections and the pathogenesis of autoimmune and other inflammatory diseases. Mast cells, key components of the innate immune system, are known for their debilitating role in allergy and autoimmune syndromes. However, their potential role in anti-microbial host defenses is increasingly being acknowledged. How mast cells interact with microbes and the nature of responses triggered thereof is not well characterized. Here we show that in response to TLR activation by Gram-positive and negative bacteria or their components like LPS, unlike macrophages, mast cells elicit pro-inflammatory but not type I IFN responses. We demonstrate that in mast cells, the bound bacteria and TLR ligands remain trapped at the cell surface and do not undergo internalization - a prerequisite for type I IFN induction. Such cells could, however, elicit type I IFNs in response to vesicular stomatitis virus (VSV), which accesses the cytosolic RIG-I receptor. Although important for anti-viral immunity, a strong type I IFN response is known to contribute to pathogenesis during bacterial infection. Thus, while endowed with the capacity to elicit type I IFNs in response to viral infection, the fact that mast cells only elicit pro-inflammatory responses upon bacterial infection illustrates that mast cells, key effector cells of the innate immune system, are well adjusted for optimal anti-bacterial and anti-viral responses. Wild type control (cntr) or interferon receptor (IFNAR)-deficient mast cells (MC) or macrophages (MAC) were infected with L.m. and S.t. (MOIs 50 and 5 for MC and MAC, respectively). MC and MAC were exposed to VSV-AV2 (MOI: 2). Samples were analyzed after 6 hours. Uninfected/unstimulated cells were used as reference samples for calculating fold change in gene expression. Gene Expression levels were determined by the Affymetrix MOE 430 2.0 GeneChips. Signal Intensities were calculated using the RMA algorithm and for statistical analysis we applied GeneSpring GX 10 software suite (Agilent Technologies, Waldbronn, Germany). MultiExperiment Viewer (MEV) software version 4.4 of the Institute for Genomic Research was used for clustering algorithm data analysis and visualization.

Dataset Information

Effect of depletion of Med23 on gene expression during VSV infection of MEF and BMDM cells.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets