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Fish & Shellfish Immunology Feb 2023Aquatic viruses can spread rapidly and widely in seawater for their high infective ability. Polyinosinic-polycytidylic acid (Poly I:C), a viral dsRNA analog, is an...
Sequencing-based network analysis provides a core set of genes for understanding hemolymph immune response mechanisms against Poly I:C stimulation in Amphioctopus fangsiao.
Aquatic viruses can spread rapidly and widely in seawater for their high infective ability. Polyinosinic-polycytidylic acid (Poly I:C), a viral dsRNA analog, is an immunostimulant that has been proved to activate various immune responses of immune cells in invertebrate. Hemolymph is a critical site that host immune response in invertebrates, and its transcriptome information obtained from Amphioctopus fangsiao stimulated by Poly I:C is crucial for understanding the antiviral molecular mechanisms of this species. In this study, we analyzed gene expression data in A. fangsiao hemolymph tissue within 24 h under Poly I:C stimulation and found 1082 and 299 differentially expressed genes (DEGs) at 6 and 24 h, respectively. Union set (1,369) DEGs were selected for subsequent analyses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were carried out for identifying DEGs related to immunity. Several significant immune-related terms and pathways, such as toll-like receptor signaling pathways term, inflammatory response term, TNF signaling pathway, and chemokine signaling pathway were identified. A protein-protein interaction (PPI) network was constructed for examining the relationships among immune-related genes. Finally, 12 hub genes, including EGFR, ACTG1, MAP2K1, and other nine hub genes, were identified based on the KEGG enrichment analysis and PPI network. The quantitative RT-PCR (qRT-PCR) was used to verify the expression profile of 12 hub genes. This research provides a reference for solving the problem of high mortality of A. fangsiao and other mollusks and provides a reference for the future production of some disease-resistant A. fangsiao.
Topics: Animals; Gene Expression Profiling; Poly I-C; Hemolymph; Transcriptome; Immunity; Computational Biology
PubMed: 36646339
DOI: 10.1016/j.fsi.2023.108544 -
Scientific Reports Jul 2023Toll-like receptor (TLR) agonists improve vaccine immunogenicity and efficacy, but they are currently unlicensed as adjuvants in influenza vaccines. This study aimed to...
Toll-like receptor (TLR) agonists improve vaccine immunogenicity and efficacy, but they are currently unlicensed as adjuvants in influenza vaccines. This study aimed to investigate whether a combination of monophosphoryl lipid A (MPL, a TLR4 agonist) and polyriboinosinic polyribocytidylic acid (poly I:C, a TLR3 agonist) can enhance the protective efficacy of an inactivated A/Puerto Rico/8/1934 (A/PR8) H1N1 influenza vaccine against homologous influenza infection and minimize illness outcomes. Results showed that combination MPL and poly I:C adjuvanted influenza vaccination increased the production of antigen-specific antibodies, decreased the levels of cytokines and cellular infiltrates at the infection sites, and induced significant memory T and B cell responses in mice. The results of this study suggest that the combination of MPL and poly I:C can be developed into a possible adjuvant for enhancing the efficacy of influenza vaccines.
Topics: Animals; Mice; Humans; Influenza Vaccines; Influenza, Human; Poly I-C; Influenza A Virus, H1N1 Subtype; Antibodies, Viral; Adjuvants, Immunologic; Immunity; Adjuvants, Pharmaceutic; Mice, Inbred BALB C
PubMed: 37507413
DOI: 10.1038/s41598-023-39210-6 -
Behavioral and Brain Functions : BBF Mar 2019Maternal immune activation (MIA) during gestation can increase the later risk of schizophrenia in adult offspring. Neuroinflammation is believed to underlie this...
BACKGROUND
Maternal immune activation (MIA) during gestation can increase the later risk of schizophrenia in adult offspring. Neuroinflammation is believed to underlie this process. Postmortem brain studies have found changes in the neuroimmune systems of patients with schizophrenia. However, little is known about the dynamic changes in cerebral inflammation and behavior during the course of the disease.
METHODS
Here, the prepulse inhibition (PPI) test was conducted in adolescent and adult Sprague-Dawley rats prenatally challenged with polyriboinosinic-polyribocytidylic acid (Poly I:C) on gestational day 9 to determine the behavioral trajectory triggered by early exposure to Poly I:C. Brain immune changes were determined in the prefrontal cortex (PFC) and hippocampus (HC) at both ages. The status of the microglia and astrocytes was determined with immunohistochemical staining. The levels of IL-6, IL-1β, and TNF-α in both brain regions were evaluated with enzyme-linked immunosorbent assays.
RESULTS
Disrupted PPI, the core phenotype of schizophrenia, only emerged in adulthood. Behavioral changes during puberty and adulthood were both accompanied by the activation of microglia (PFC and HC). Astrocytes were only activated at PN60. The levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) in the offspring of the Poly I:C-exposed mothers differed with brain region and time, with more cytokines elevated during periadolescence than during adulthood.
CONCLUSIONS
Our findings indicate that immune activation emerged before symptom manifestation in the offspring of MIA rats. We conclude that early prenatal Poly I:C challenge can lead to age-related behavioral and neuroinflammatory changes. These data provide new insight into the neuroinflammatory and neuropathological mechanisms underlying the development of schizophrenia. They also suggest that periadolescence could be more important than adulthood in the prevention and treatment of schizophrenia.
Topics: Age Factors; Animals; Behavior, Animal; Brain; Disease Models, Animal; Female; Hippocampus; Male; Microglia; Neuroimmunomodulation; Poly I-C; Prefrontal Cortex; Pregnancy; Prenatal Exposure Delayed Effects; Prepulse Inhibition; Rats; Rats, Sprague-Dawley
PubMed: 30836963
DOI: 10.1186/s12993-019-0154-2 -
American Journal of Reproductive... Jul 2005Natural killer (NK) cells were associated with first trimester embryo loss. The current study in the inbred F344 rat assessed the role of NK cells in mediating...
PROBLEM
Natural killer (NK) cells were associated with first trimester embryo loss. The current study in the inbred F344 rat assessed the role of NK cells in mediating resorptions caused by poly I-C, a non-specific immunostimulator.
METHOD OF STUDY
On fifth day of gestation, rats were injected intraperitoneally with anti-NKR-P1 (1.5 mg/kg, i.p.) to deplete NK cells, and with mouse serum or saline to control for non-specific effects. Poly I-C (4 mg/kg, i.p.) or vehicle were administered 2 days later. Resorptions were assessed on day 13.5.
RESULTS
Poly I-C significantly elevated resorption rates, and anti-NKR-P1 abolished this effect. Body weight was reduced in all rats treated with poly I-C, including NK-depleted rats. This indicates the ability of NK-depleted rats to respond to poly I-C, yet to refrain from the resorption-promoting effects of poly I-C.
CONCLUSIONS
This study suggests a role for NK cells in mediating poly I-C-induced resorptions.
Topics: Animals; Body Weight; Embryo Loss; Female; Killer Cells, Natural; Poly I-C; Pregnancy; Rats; Rats, Inbred F344; Time Factors
PubMed: 15948772
DOI: 10.1111/j.1600-0897.2005.00286.x -
Acta Pharmacologica Sinica Oct 2012To examine the neuroprotective effects of the Toll-like receptor 3 (TLR3) agonist Poly I:C in acute ischemic models in vitro and in vivo.
AIM
To examine the neuroprotective effects of the Toll-like receptor 3 (TLR3) agonist Poly I:C in acute ischemic models in vitro and in vivo.
METHODS
Primary astrocyte cultures subjected to oxygen-glucose deprivation (OGD) were used as an in vitro simulated ischemic model. Poly I:C was administrated 2 h before OGD. Cell toxicity was measured using MTT assay and LDH leakage assay. The levels of TNFα, IL-6 and interferon-β (IFNβ) in the media were measured using ELISA. Toll/interleukin receptor domain-containing adaptor-inducing IFNβ (TRIF) protein levels were detected using Western blot analysis. A mouse middle cerebral artery occlusion (MCAO) model was u sed for in vivo study. The animals were administered Poly I:C (0.3 mg/kg, im) 2 h before MCAO, and examined with neurological deficit scoring and TTC staining. The levels of TNFα and IL-6 in ischemic brain were measured using ELISA.
RESULTS
Pretreatment with Poly I:C (10 and 20 μg/mL) markedly attenuated OGD-induced astrocyte injury, and significantly raised the cell viability and reduced the LDH leakage. Poly I:C significantly upregulated TRIF expression accompanied by increased downstream IFNβ production. Moreover, Poly I:C significantly suppressed the pro-inflammatory cytokines TNFα and IL-6 production. In mice subjected to MCAO, administration of Poly I:C significantly attenuated the neurological deficits, reduced infarction volume, and suppressed the increased levels of TNFα and IL-6 in the ischemic striatum and cortex.
CONCLUSION
Poly I:C pretreatment exerts neuroprotective and anti-inflammatory effects in the simulated cerebral ischemia models, and the neuroprotection is at least in part due to the activation of the TLR3-TRIF pathway.
Topics: Animals; Astrocytes; Blotting, Western; Cell Culture Techniques; Cell Survival; Cells, Cultured; Culture Media; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Glucose; Ischemic Attack, Transient; Mice; Neuroprotective Agents; Oxygen; Poly I-C; Rats; Rats, Sprague-Dawley; Toll-Like Receptor 3
PubMed: 22983393
DOI: 10.1038/aps.2012.122 -
Neuroscience Letters Jan 2011Viral infections are frequently found in opioid addicts, subjecting them to immune challenge. However, the effects of immune challenge on opioid withdrawal are not fully...
Viral infections are frequently found in opioid addicts, subjecting them to immune challenge. However, the effects of immune challenge on opioid withdrawal are not fully understood. In the present study, mice were intraperitoneally injected with 2mg/kg polyinosinic-polycytidylic acid (Poly I:C, a viral mimetic) for 3 days to induce an immune challenge, followed by subcutaneous injection of morphine 3 times per day for 3 days to induce morphine dependence. Withdrawal was induced by an intraperitoneal injection of 5mg/kg naloxone, an opioid receptor antagonist. The results showed that Poly I:C pretreatment did not alter body weight loss, jumping behavior, or locomotion during naloxone-precipitated withdrawal. In contrast, Poly I:C pretreatment significantly increased immobility time in the tail suspension test. Our findings suggest that Poly I:C-induced immune challenge has no effects on acute physical opioid withdrawal symptoms but facilitates depression-like behavior.
Topics: Animals; Behavior, Animal; Interferon Inducers; Mice; Morphine Dependence; Naloxone; Narcotic Antagonists; Poly I-C; Substance Withdrawal Syndrome
PubMed: 20974220
DOI: 10.1016/j.neulet.2010.10.052 -
Fish & Shellfish Immunology Dec 2022Red-spotted grouper (Epinephelus akaara) is a popular aquaculture species with high commercial value in the food industry. However, some infectious diseases may cause...
Red-spotted grouper (Epinephelus akaara) is a popular aquaculture species with high commercial value in the food industry. However, some infectious diseases may cause mass mortality in cultural practice. Therefore, it is important to understand the immune responses of red-spotted groupers upon pathogenic invasion to develop successful disease prevention mechanisms. Here, we analyzed the transcriptomic profiles of red-spotted grouper head kidney stimulated with lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (poly I:C), and nervous necrosis virus (NNV) and identified differentially expressed genes (DEGs) using RNA-sequencing technology. Cluster analysis of the identified DEGs showed DEG distribution in nine separate clusters based on their expression patterns. However, significant upregulation of most DEGs was observed 6 h after poly I:C stimulation. The DEGs were functionally annotated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, which revealed significant expression of many immune-related signaling pathways, including antiviral, protein translation, cellular protein catabolic process, inflammatory responses, DNA repair, and cell division. Furthermore, selected DEGs were validated by quantitative real-time PCR, confirming the reliability of our findings. Collectively, this study provides insight into the immune responses of red-spotted groupers, thereby expanding the understanding of fish immunity.
Topics: Animals; Bass; Lipopolysaccharides; RNA-Seq; Reproducibility of Results; Fish Diseases; Nodaviridae; Poly I-C; Transcriptome; Necrosis; Fish Proteins; RNA Virus Infections
PubMed: 36356858
DOI: 10.1016/j.fsi.2022.11.006 -
Journal of Visualized Experiments : JoVE Aug 2022Maternal immune activation (MIA) during pregnancy is consistently linked to increased risk of neurodevelopmental and neuropsychiatric disorders in offspring. Animal...
Maternal immune activation (MIA) during pregnancy is consistently linked to increased risk of neurodevelopmental and neuropsychiatric disorders in offspring. Animal models of MIA are used to test causality, investigate mechanisms, and develop diagnostics and treatments for these disorders. Despite their widespread use, many MIA models suffer from a lack of reproducibility and almost all ignore two important aspects of this risk factor: (i) many offspring are resilient to MIA, and (ii) susceptible offspring can exhibit distinct combinations of phenotypes. To increase reproducibility and model both susceptibility and resilience to MIA, the baseline immunoreactivity (BIR) of female mice before pregnancy is used to predict which pregnancies will result in either resilient offspring or offspring with defined behavioral and molecular abnormalities after exposure to MIA. Here, a detailed method of inducing MIA via intraperitoneal (i.p.) injection of the double stranded RNA (dsRNA) viral mimic poly(I:C) at 12.5 days of gestation is provided. This method induces an acute inflammatory response in the dam, which results in perturbations in brain development in mice that map onto similarly impacted domains in human psychiatric and neurodevelopmental disorders (NDDs).
Topics: Animals; Behavior, Animal; Disease Models, Animal; Female; Humans; Mice; Poly I-C; Pregnancy; Prenatal Exposure Delayed Effects; Reproducibility of Results
PubMed: 36063000
DOI: 10.3791/64095 -
Japanese Journal of Microbiology Apr 1976Seven polyinosinic-polycytidylic acid (poly I-poly C) preparations, ranging from 4.2 S to 21.2 S, prepared from various sizes of polyinosinate and polycytidylate, were... (Comparative Study)
Comparative Study
Seven polyinosinic-polycytidylic acid (poly I-poly C) preparations, ranging from 4.2 S to 21.2 S, prepared from various sizes of polyinosinate and polycytidylate, were examined for toxicity and interferon-inducing activity in mice. The increase in size of poly I-poly C was accompanied by increases both in the maximal amount of interferon produced and in the length of persistence of a high level of interferon in plasma. Toxicity of poly I-poly C was proportional to the molecular size within the range of 8 S to 16 S. The amount of interferon induced by 1/5 LD50 of poly I-poly C depended on the size of the inducer, being increasingly lower with progressively smaller sizes. Next, activities of poly I-poly C in culture cells were examined. The resistance-inducing activity of poly I-poly C in primary chick embryo cells (CEC) increased with the size of the inducer (4.2 S to 11.6 S), whereas the activity in L cells was not so markedly dependent upon its molecular size as in CEC. In the presence of calf serum during induction of resistance the activity was lowered. The activities of preparations with small molecular sizes were affected by calf serum more markedly than those of large molecular sizes. The interferon-inducing activity in RK13 was not appreciably influenced by the size of poly I-poly C, especially in the presence of DEAE-dextran, while the activity in L cells was markedly dependent upon the size of the inducer. These results suggest that the influence of the molecular size of poly I-poly C upon the resistance-inducing and interferon-inducing activities varies among different kinds of cells, and alters in the presence of serum or DEAE-dextran.
Topics: Animals; Cell Line; Chick Embryo; Culture Techniques; Interferons; L Cells; Lethal Dose 50; Male; Mice; Poly I-C
PubMed: 948145
DOI: 10.1111/j.1348-0421.1976.tb00911.x -
World Journal of Gastroenterology Feb 2017To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis.
AIM
To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium (DSS)-induced acute colitis.
METHODS
Thirty C57BL/6 mice were given either regular drinking water (control group) or 2% (w/v) DSS drinking water (model and poly I:C groups) for 7 d. Poly I:C was administrated subcutaneously (20 μg/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin 17 (IL-17) and interferon-γ (IFN-γ). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeled-dextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction (TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (RT-qPCR).
RESULTS
DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The mRNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-qPCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-α, IL-17 and IFN-γ.
CONCLUSION
Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.
Topics: Animals; Colitis, Ulcerative; Colon; Cytokines; Dextran Sulfate; Disease Models, Animal; Fluorescent Antibody Technique; Immunity, Innate; Immunohistochemistry; Injections, Subcutaneous; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Permeability; Peroxidase; Poly I-C; Real-Time Polymerase Chain Reaction; Severity of Illness Index; Tight Junction Proteins; Toll-Like Receptor 3; Weight Loss
PubMed: 28246473
DOI: 10.3748/wjg.v23.i6.999