IL-1B signaling in dendritic cells induces antiviral interferon responses
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PROVIDER: PRJNA429565 | ENA |
REPOSITORIES: ENA
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Project description:Activation of interferon-stimulated gene (ISG) responses is critical for control of viral infection. We recently identified that stimulation of the NLRP3 inflammasome and mobilization of the inflammatory cytokine IL-1β act as critical host restrictive pathways against West Nile virus (WNV) in a mechanism dependent on the regulation of ISGs. In order to define the mechanism by which IL-1β regulates these antiviral immune programs, we utilized global transcriptome analysis in myeloid cells, known targets of WNV replication to define gene signatures required for IL-1β driven antiviral responses. Surprisingly, we found IL-1β dependent activation of interferon-beta (IFN-β) and ISGs at late times following IL-1β treatment. Expression of these antiviral innate immune genes was found to be dependent on activation of IRF3 and appears to reflect a general shift in IL-1β signaling from an inflammatory response early following treatment to an anti-inflammatory type-I IFN mediated response at later times post-treatment. These data demonstrate that inflammatory and antiviral signals integrate to control viral infection. Strategies to co-opt these cytokine activated antiviral signatures can act as novel targeted therapeutic strategies tailored specifically to individual pathogens.
2018-01-12 | GSE109069 | GEO
Project description:Systemic lupus erythematosus (SLE) is characterized by upregulation of Type Ι Interferon (IFN) and widespread inflammation. However, blocking the IFN pathway benefits a fraction of patients, pointing to additional pathogenic players. Here we describe monocytes (Mo) undergoing erythrophagocytosis and co-expressing IFN-inducible genes (ISGs) and interleukin-1b (IL-1b) in patients with active disease. This phenotype is recapitulated in vitro upon internalization of red blood cells carrying mitochondria (Mito+ RBCs), a feature of SLE. While ISG expression requires the interaction between Mito+ RBC-derived mitochondrial DNA (mtDNA) and cGAS, the production of IL-1b entails Mito+ RBC-derived mitochondrial RNA (mtRNA) triggering RIG-I-like receptor (RLR) activation. This leads to the cytosolic release of Mo-derived mtDNA and activation of the NLRP3 inflammasome. Importantly, the Type I IFN-inducible protein myxovirus resistant protein 1 (MxA) enables IL-1b release by routing this cytokine into a trans-Golgi network (TGN)-mediated unconventional secretory pathway. As Type I IFN and IL-1b are thought to counter-regulate each other, our study highlights an unprecedented synergy between these two cytokine pathways in SLE.
2024-10-07 | GSE211361 | GEO
Project description:U3A cells stably expressing wild-type STAT1 or STAT1-CC were treated with interferon beta (10U/ml) or control for 24 hours to assess effects of stat1 modifications, interferon, and the interaction on gene expression. Keywords: interferon, STAT1, STAT1-CC, STAT1CC, STAT-1C, antiviral RNA was isolated from stable U3A-STAT1 lines stably expressing wild-type STAT1 or STAT1CC, after 24 hour treatment with interferon beta (10U/ml) or control.
2015-09-01 | E-GEOD-61413 | biostudies-arrayexpress
Project description:Type I Interferon promotes MxA-dependent IL-1b release in SLE monocytes
| PRJNA869965 | ENA
Project description:Dendritic cells (DC) serve a key function in host defense, linking innate detection of microbes to the activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of HIV-1 by host innate pattern-recognition receptors and subsequent coupling to antiviral T cell responses is not yet known. DC are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement. We show here that, when DC resistance to infection is circumvented, HIV-1 induces DC maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly-synthesized HIV-1 capsid (CA) with cellular cyclophilin A (CypA) and the subsequent activation of the transcription factor IRF3. Because the peptidyl-prolyl isomerase CypA also interacts with CA to promote HIV-1 infectivity, our results suggest that CA conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell intrinsic sensor for HIV-1 exists in DC and mediates an antiviral immune response, but it is not typically engaged due to absence of DC infection. The virulence of HIV-1 may be related to evasion of this response, whose manipulation may be necessary to generate an effective HIV-1 vaccine. We analyzed the gene expression profiles of uninfected human monocyte-derived dendritic cells (MDDCs) and MDDCs infected with an envelope-defective GFP-encoding VSV-G-pseudotyped HIV-1 vector (HIVGFP(G)) and with VSV-G pseudotyped virus-like particles derived from SIVmac to deliver Vpx (SIVVLP(G)), alone or in combination. Cells were infected at day 4 of differentiation and cells were harvested 48 hours later. RNA was extracted with TRIzol. RNA was labeled and hybridized to Human Genome U133A 2.0 arrays arrays following the Affymetrix protocols. Data were analyzed in R and Bioconductor.
2010-09-09 | E-GEOD-22589 | biostudies-arrayexpress
Project description:Interleukin 1b and interferon g are two cytokines that are central to the inflammatory response. They both have a broad range of activity, each directing the immune response to be towards either the innate response (IL-1b and IFN-g) or the cellular response (IFN-g), however invivo there is a lot of subtle interactions. Microarray analysis has been used to characterize the transcriptional response to recombinant rainbow trout IL-1b and IFN-g in a rainbow trout macrophage cell line RTS-11. The use of the cell line removes the host response and the interference of other cellular factors that occur when performing whole fish experiments, or even primary cultures. RNA was extracted from stimulated or control cells following 6h incubation, this was used to hybridize to a 16K v1 salmonid cDNA array constructed by GRASP consortium. Keywords: Dual label cDNA microarray
2007-06-16 | GSE5091 | GEO
Project description:IL-1B is an important cytokine that is often found to be up-regulated during osteoarthritic and rheumatoid joint diseases. It is viewed as a catabolic factor, inducing enzymes that allow for the degradation of the cartilage extracellular matrix and also has essential roles as an autocrine and paracrine factor in fibronectin fragment-mediated degradation. It can also reduce the synthesis of the major cartilage components, type II collagen and aggrecan. On the other hand, IL-1B also has the ability to induce the growth and morphogenic factor BMP-2. During joint diseases, IL-1B is synthesized by both synovial cells and chondrocytes. Addition of IL-1 biological antagonists such as IL-1 receptor antagonists can suppress cartilage degradation in vitro. Thus, the production of IL-1B could act as the first step in mediating a cascade of other mediators in cartilage which could be relevant to the fate of the cartilage. In order to obtain a global picture of the effect of IL-1B production on human adult articular chondrocytes, we analyzed changes in gene expression induced by IL-1B by microarray analysis. We found that IL-1B has a diverse effect on gene expression profile in chondrocytes. One of the predominant responses that we observed in adult human articular chondrocytes on exposure to IL-1B is a dramatic increase in a large set of chemokines and other genes related to the inflammatory cascade. Keywords: Gene response to IL-1B (10 ng/ml) Cartilage was obtained from adult human tissue donors with above the knee amputations due to chondrosarcoma or traumatic injury or from autopsy. Chondrocytes were isolated following established protocols, maintained in high density, and treated with IL-1B (10 ng/ml). Chondrocytes treated with buffer only served as the untreated control. The experiment was carried out in duplicate. Total RNA was extracted from these chondrocytes, labeled with fluorophores (Cy3 or Cy5) and analyzed for expression changes using the Human Operon/Qiagen v3.0 oligonucleotide array. The analysis was repeated with the fluorophore dyes exchanged between the untreated and experimental RNAs.
2008-05-14 | E-GEOD-11427 | biostudies-arrayexpress
Project description:Allergens Elicit an Antiviral Signature in Dendritic Cells
| PRJNA755636 | ENA
Project description:IL-1B is an important cytokine that is often found to be up-regulated during osteoarthritic and rheumatoid joint diseases. It is viewed as a catabolic factor, inducing enzymes that allow for the degradation of the cartilage extracellular matrix and also has essential roles as an autocrine and paracrine factor in fibronectin fragment-mediated degradation. It can also reduce the synthesis of the major cartilage components, type II collagen and aggrecan. On the other hand, IL-1B also has the ability to induce the growth and morphogenic factor BMP-2. During joint diseases, IL-1B is synthesized by both synovial cells and chondrocytes. Addition of IL-1 biological antagonists such as IL-1 receptor antagonists can suppress cartilage degradation in vitro. Thus, the production of IL-1B could act as the first step in mediating a cascade of other mediators in cartilage which could be relevant to the fate of the cartilage. In order to obtain a global picture of the effect of IL-1B production on human adult articular chondrocytes, we analyzed changes in gene expression induced by IL-1B by microarray analysis. We found that IL-1B has a diverse effect on gene expression profile in chondrocytes. One of the predominant responses that we observed in adult human articular chondrocytes on exposure to IL-1B is a dramatic increase in a large set of chemokines and other genes related to the inflammatory cascade. Keywords: Gene response to IL-1B (10 ng/ml)
2008-05-14 | GSE11427 | GEO
Project description:Induction of interferon beta (IFN-β), IFN-stimulated genes (ISGs), and inflammatory responses is critical for control of viral infection. We recently identified an essential linkage of stimulation of the inflammatory cytokine interleukin-1β (IL-1β) and induction of ISGs that function as host restriction pathways against the emerging flavivirus West Nile virus (WNV) in vivo Here we utilized ex vivo global transcriptome analysis of primary dendritic cells, known targets of WNV replication, to define gene signatures required for this IL-1β-driven antiviral response. Dendritic cells that were deficient in IL-1 receptor signaling showed dysregulation of cell-intrinsic defense genes and loss of viral control during WNV infection. Surprisingly, we found that in wild-type cells, IL-1β treatment, in the absence of infection, drove the transcription of IFN-β and ISGs at late times following treatment. Expression of these antiviral innate immune genes was dependent on the transcription factor IFN regulatory factor 3 (IRF3) and appears to reflect a general shift in IL-1β signaling from an early inflammatory response to a late IFN-mediated response. These data demonstrate that inflammatory and antiviral signals integrate to control viral infection in myeloid cells through a process of IL-1β-to-IRF3 signaling crosstalk. Strategies to exploit these cytokines in the activation of host defense programs should be investigated as novel therapeutic approaches against individual pathogens.IMPORTANCE West Nile virus is an emerging mosquito-borne flavivirus that can result in serious illness, neuropathology, and death in infected individuals. Currently, there are no vaccines or therapies for human use against West Nile virus. Immune control of West Nile virus infection requires inflammatory and antiviral responses, though the effect that each arm of this response has on the other is unclear. The significance of our research is in defining how virus-induced inflammatory responses regulate critical antiviral immune programs for effective control of West Nile virus infection. These data identify essential mechanisms of immune control that can inform therapeutic efforts against West Nile virus, with potential efficacy against other neuroinvasive viruses.
| S-EPMC5874908 | biostudies-literature