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PROVIDER: PRJNA1311247 | ENA |
REPOSITORIES: ENA
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Project description:The Mechanism of PEDV-Induced Exosomes from Intestinal Epithelial Cells Inhibiting Macrophage Migration and Phagocytic Function_total_RNAseq
| PRJNA1308867 | ENA
Project description:Virus-induced inflammation has long served as a canonical hallmark of host immune activation. Paradoxically, the same pathogen can sculpt an immunosuppressive milieu that accelerates its own dissemination. Here we show that, although porcine epidemic diarrhea virus (PEDV) rapidly triggers intestinal epithelial cells to secrete pro-inflammatory cytokines and chemokines—thereby amplifying epithelial–macrophage crosstalk and engaging RIG-I and Toll-like receptor signaling in macrophages—the cells’ phagocytic, endocytic, and lysosomal effector pathways are markedly repressed. Mechanistic dissection revealed that PEDV-infected epithelial cells release exosomes that potently inhibit macrophage migration and phagocytosis. Exosomal miR-190a, induced by PEDV, targets tropomodulin-3 (TMOD3), disrupting actin capping, reducing cellular stiffness and adhesion, and consequently impairing macrophage motility. Concomitantly, PEDV-induced exosomal lncRNA TS-2083 binds ANXA2, facilitating its ubiquitin-dependent degradation and disrupting phagocytic-cup formation, thereby attenuating macrophage engulfment. Notably, after oral PEDV challenge, piglet serum contains circulating exosomes enriched in miR-190a and lncRNA TS-2083 that recapitulate the same inhibitory effects on macrophage migration and phagocytosis. Our findings reposition PEDV immune evasion from “interferon antagonism” to “cross-cell communication reprogramming,” providing a new theoretical framework and translational roadmap for dissecting pathogenesis and designing host-directed interventions against porcine coronaviruses and other mucosa-tropic viruses.
2025-10-14 | PXD069460 |
Project description:Porcine epidemic diarrhea virus (PEDV) causes severe intestinal damage and high mortality in neonatal piglets. The continuous emergence of new strains has brought new challenges to prevention and control. In this study, we isolated and characterized a prevalent PEDV virulent strain, and analyzed 19,612 jejunal cells from PEDV-infected and control piglets using single-cell sequencing, revealing significant changes in cellular composition, gene expression, and intercellular communication. In response to PEDV infection, epithelial repair was enhanced through increased proliferation and differentiation of stem cells, transit-amplifying (TA) cells, and intestinal progenitor cells into enterocytes. Additionally, PEDV disrupted intercellular communication, compromising epithelial functionality while triggering immune responses, with IFN-II and IL-10 signaling activation acting as critical regulators of immune balance and tissue homeostasis. Beyond enterocytes, viral genes were detected in various other cell types. Further experiments confirmed that PEDV could initiate replication in B and T lymphocytes but was unable to produce infectious progeny, with T cells additionally undergoing virus-induced apoptosis. These findings provide new insights into PEDV tropism, immune evasion, and epithelial repair, revealing complex host-pathogen interactions that shape disease progression and tissue regeneration, thereby contributing to a better understanding of enteric coronavirus pathogenesis.
2025-04-22 | GSE293713 | GEO
Project description:Porcine epidemic diarrhea virus (PEDV) has reemerged as the main pathogen of piglets due to its high mutation feature. Monolaurin (ML) is a natural compound with a wide range of antibacterial and antiviral activities. However, the role of ML in PEDV infection is still unknown. This study aimed to evaluate the effect of ML on the growth performance, intestinal function, virus replication and cytokine response in piglets infected with PEDV, and to reveal the mechanism through proteomics analysis. Piglets were orally administrated with ML at a dose of 100 mg/kg·BW for 7 days before PEDV infection. Results showed that although there was no significant effect on the growth performance of piglets, ML administration alleviated the diarrhea caused by PEDV infection. ML administration promoted the recovery of intestinal villi, thereby improving intestinal function. Meanwhile, PEDV replication was significantly inhibited, and PEDV-induced expression of IL-6 and IL-8 were decreased with ML administration. Proteomics analyses showed that 38 proteins were differentially expressed between PEDV and ML+PEDV groups, and were significantly enriched in the interferon-related pathways. This suggests ML could promote the restoration of homeostasis by regulating the interferon pathway. Overall, the present study demonstrated ML could confer a protective effect against PEDV infection in piglets, and may be developed as a drug or feed additive to prevent and control PEDV disease.
2022-02-16 | PXD029561 | Pride
Project description:Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic virus that causes severe gastrointestinal disease in neonatal piglets, often leading to high mortality. To advance the study of viral pathogenesis, it is essential to develop an in vitro model that accurately replicates swine enteric coronavirus infections. In this study, we designed a porcine intestinal apical-out organoid culture system that supports viral replication while allowing for long-term culture and experimental manipulation. Using apical-out organoids derived from the duodenum, jejunum, and ileum, we examined region-specific gene expression profiles in response to PEDV infection. Bulk RNA sequencing revealed distinct gene expression patterns, highlighting the regional differences in intestinal physiology during infection. Differential gene expression analysis indicated that each intestinal segment activates specific signaling pathways related to cell survival and antiviral responses following PEDV infection. Functional analyses identified key pathways involved in cell development, signaling, apoptosis, and survival. This study elucidates the mechanisms underlying the differential responses of specific intestinal regions to PEDV, which may inform the selection of optimal models for future PEDV research. In summary, our systematic investigation into the responses of various small intestine segments following PEDV infection provides deeper insights into viral pathogenesis.
2024-12-31 | GSE280630 | GEO
Project description:The immune system is thought to be fragile in the neonate, which is susceptible to pathogens. Exosomes are a type of vehicles existing in the body fluid and participate in many biological processes, especially the immune response. Inorder to investigate the roles that exosomes may play during virus infection in the neonate, porcine epidemic diarrhea virus (PEDV), a devastating enteric virus to newborn piglets, was selected for infection. Serum exosomes were then isolated from the newborn-piglets infected or mock-infected with PEDV and followed by a label-free LC-MS/MS based comparative quantitative proteomic analysis. Among 441 proteins detected in the serum exosomes, there were lots of complement proteins. The expression level of the complement C3, C6 and CFB suffered drastic changes due to PEDV infection. After the confirmation by western-blot assay, we then investigated the function of these exosomes on PEDV infection and discovered that the exosomes from mock-infected newborn piglets restricted PEDV infection but this inhibition disappeared after exosomes were heat-inactivated, suggesting that the complement is one of the key antiviral molecules. These findings will facilitate the understanding of the antiviral response of the neonate mediated by exosomes
2019-04-30 | PXD010762 | Pride
Project description:Glioblastoma (GBM) remains a challenging malignancy with dismal prognoses despite aggressive treatment regimens. Intratumoral heterogeneity contributes to therapeutic resistance, with roles for stem cell-like brain tumor initiating cells (GBMs), glioma associated macrophages (GAMs), and communication between them. GAMs are derived from infiltrating lymphocytes, and monocyte migration is increased by GBM cell release of extracellular vesicles, including exosomes. GBM survival is promoted by the glucose transporter GLUT3, which was recently shown to alter macrophage activation states. We found that GBM-derived exosomes contain GLUT3 and that exosomes from GLUT3 expressing GBMs significantly increased monocyte migration in comparison to controls. Monocytes transfected with GLUT3 (but not GLUT1) also had significantly increased migration, demonstrating a direct role for GLUT3 in monocytes migration. Analysis of the transcriptome of exosome treated monocytes demonstrated that exosomes derived from GLUT3 expressing GBMs increasedGDF-15in monocytes. GDF-15 is a known regulator of monocyte migration, and we determined that knockdown of GDF-15 blocked the migration induced by GBM-derived exosomes. As GDF-15 induced monocyte migration is thought to involve MMP12, we next evaluated MMP12 as a potential mediator of the pro-migratory phenotype.MMP12was significantly increased in monocytes upon treatment with exosomes derived from GLUT3 expressing GBMs as was MMP12 activity. Together, our findings suggest a novel mechanism by which GBMs facilitate immune evasion and tumor progression: GBM-derived exosomes transfer GLUT3 to monocytes to increase a GDF-15/MMP12 pathway that promotes monocyte migration. The data also highlight the importance of understanding and targeting cell-cell interactions to improve glioblastoma treatment.
2024-12-01 | GSE274966 | GEO
Project description:Previously we have described the role of liver stellate cell exosomes in triggering macrophage migration and immune activation, we wanted to study what cargo in this exosomes were responsible for such activation. We found a few interesting mRNAs and siRNAs involved in the immune response pathway and cytokine production. We have found that Ectodysplasin A, a hepatokine, has an important role in stimulating the macrophage response and to be highly expressed in liver cirrhosis.
2022-01-31 | E-MTAB-11373 | biostudies-arrayexpress