IRF-3

In mice, adenovirus (Ad)-elicited IFN-ab mediates the overproduction of LPS stimulated cytokines such as TNFa and IL-6. We found that Ad infection also mediates the overproduction of IFN-ab itself and enables its production in splenic marginal zone macrophages, which don't produce IFN-ab in response to LPS alone. We show the importance of the scavenger receptor MARCO for Ad uptake and cytokine overproduction in vivo, and the differential contribution of infection and rIFN-b to LPS-induced cytokine response in macrophage subsets...

Exposure to Cr and/or Ni can have widespread implications on the environment and health. However, the specific toxic effects of chronic Cr and Ni co-exposure on mice liver have not been reported. To ascertain the combined toxic effects of chronic Cr and Ni co-exposure on liver damage in mice, 80 6-week-old female C57BL/6 J mice were randomly divided into 4 groups: the Con group, Cr group (Cr+6 50 mg/L), Ni group (Ni+2 110 mg/L), and Cr + Ni group (Cr+6 50 mg/L + Ni+2 110 mg/L)...

Narciclasine is an alkaloid belonging to the Amaryllidaceae family which has been reported to have many beneficial properties. Especially its anticancer properties have been widely reported. Here, we have focused on its potential use in suppressing the inflammatory response in sepsis using in silico methods. Lipopolysaccharide (LPS) is an endotoxin which is present in the outer membrane of gram-negative bacteria and is a crucial player in the pathogenesis of gram-negative sepsis. Activation of toll-like receptor 4 (TLR4) signaling by LPS is an important event in the pathogenesis of gram-negative sepsis...

Bovine viral diarrhea virus (BVDV) has caused massive economic losses in the cattle business worldwide. Fatty acid synthase (FASN), a key enzyme of the fatty acid synthesis (FAS) pathway, has been shown to support virus replication. To investigate the role of fatty acids (FAs) in BVDV infection, we infected CD8+ T lymphocytes obtained from healthy cattle with BVDV in vitro. During early cytopathic (CP) and noncytopathic (NCP) BVDV infection in CD8+ T cells, there is an increase in de novo lipid biosynthesis, resulting in elevated levels of free fatty acids (FFAs) and triglycerides (TG)...

Influenza A and B viruses overcome the host antiviral response to cause a contagious and often severe human respiratory disease. Here, integrative structural biology and biochemistry studies on non- structural protein 1 of influenza B virus (NS1B) reveal a previously unrecognized viral mechanism for innate immune evasion. Conserved basic groups of its C-terminal domain (NS1B-CTD) bind 5'- triphosphorylated double-stranded RNA (5'ppp-dsRNA), the primary pathogen-associated feature that activates the host retinoic acid-inducible gene I protein (RIG-I) to initiate interferon synthesis and the cellular antiviral response...

This experiment was conducted to explore the effects of dietary synbiotics supplementation on growth performance, immune function, and intestinal barrier function in piglets challenged with PEDV. Forty crossbred (Duroc × Landrace × Yorkshire) weaned piglets (26 ± 1 day-old) with a mean body weight of 6.62 ± 0.36 kg were randomly allotted to five groups: Control (CON) I and CONII group, both fed basal diet; 0.1% synbiotics (SYB) group, 0.2% SYB group and 0.2% yeast culture (YC) group, fed basal diet supplemented with 0...

The current study investigated the potential effects of probiotic supplementation on colorectal carcinogenesis chemically induced with 1,2-dimethylhydrazine (DMH) and treated with 5-fluorouracil (5FU)-based chemotherapy in mice. Animals were randomly allocated in five different groups: Control: which not receive any treatment throughout the experimental course; Colitis model group (DMH): treated with DMH; DMH+ 5FU: animals received I.P. (intraperitoneal) dose of chemotherapy on a weekly basis; DMH+PROB: animals received daily administrations (via gavage) of probiotics (Lactobacillus: acidophilus and paracasei, Bifidobacterium lactis and bifidum); and DMH+ PROB+ 5FU: animals received the same treatment as the previous groups...

SARS-CoV-2 triggered the global COVID-19 pandemic, posing a severe threat to public health worldwide. The innate immune response in cells infected by SARS-CoV-2 is primarily orchestrated by type I interferon (IFN), with IFN-β exhibiting a notable inhibitory impact on SARS-CoV-2 replication. FHL2 , acting as a docking site, facilitates the assembly of multiprotein complexes and regulates the transcription of diverse genes. However, the association between SARS-CoV-2 and FHL2 remains unclear. In this study, we report for the first time that SARS-CoV-2 infection in Caco2 cells results in the upregulation of FHL2 expression, while the virus's N proteins can enhance FHL2 expression...

Swine flu caused by swine influenza A virus (swIAV) is an acute respiratory viral disease that is spreading in swine herds worldwide. Although the effect of some host factors on replication of swIAV has been identified, the role of CD46 in this process is unclear. Here, we report that CD46 inhibits the replication of swIAV by promoting the production of type I interferons (IFNs) in porcine kidney (PK-15) cells. CD46 knockout (CD46-KO) and stably expressing (CD46-overexpression) PK-15 cells were prepared using lentivirus-mediated CRISPR/Cas9 gene editing and seamless cloning technology...

Anguillid herpesvirus 1 (AngHV), the causative agent of "mucus sloughing and hemorrhagic septicemia disease", causes serious infectious diseases in farmed eel. Among the effective prevention and control strategies, vaccination is one of the most effective approaches. However, no vaccine for AngHV is available. Our study developed a formalin-inactivated AngHV vaccine and evaluated its performance in American eels. Initially, AngHV-FJ, a strain of AngHV, was inactivated completely by 0.1 % formaldehyde, mixed with adjuvant Montanide ISA 763 A VG (763A)...

BACKGROUND: Activated-platelets secrete platelet factor-4 (PF4), which contributes to the viral pathogenesis. Recently, we reported the pro-viral role of PF4 on replication of closely related flaviviruses, Japanese encephalitis virus (JEV) and dengue virus (DENV). OBJECTIVE: This study investigated the detailed mechanism of PF4-mediated virus replication. METHODS: PF4-/- or wild-type (WT) mice were infected with JEV and host-defense mechanisms including autophagic/interferon (IFN)-responses were assessed...

HIV infection impairs host immunity, leading to progressive disease. An anti-retroviral treatment efficiently controls viremia but cannot completely restore the immune dysfunction in HIV-infected individuals. Both host and viral factors determine the rate of disease progression. Among the host factors, innate immunity plays a critical role; however, the mechanism(s) associated with dysfunctional innate responses are poorly understood among HIV disease progressors, which was investigated here. The gene expression profiles of TLRs and innate cytokines in HIV-infected (LTNPs and progressors) and HIV-uninfected individuals were examined...

Type I interferon-beta (IFN-β) is a crucial component of innate and adaptive immune systems inside the host. The formation of bacterial biofilms on medical implants can lead to inflammatory diseases and implant failure. Biofilms elicit IFN-β production inside the host that, in turn, restrict bacterial growth. Biofilms pose strong antibiotic resistance, whereas surface modification of medical implants with antibacterial agents may demonstrate strong antimicrobial effects. Most of the previous investigations were focused on determining the antibacterial activities of implant surfaces modified with antibacterial agents...

During the replication of viral genomes, RNA viruses produce double-stranded RNA (dsRNA), through the activity of their RNA-dependent RNA polymerases (RdRps) as viral replication intermediates. Recognition of viral dsRNA by host pattern recognition receptors - such as retinoic acid-induced gene-I (RIG-I)-like receptors and Toll-like receptor 3 (TLR3) - triggers the production of interferon (IFN)-β via the activation of IFN regulatory factor (IRF)-3. It has been proposed that, during the replication of viral genomes, each of RIG-I and melanoma differentiation-associated gene 5 (MDA5) form homodimers for the efficient activation of a downstream signaling pathway in host cells...

Tripartite motif 21 (TRIM21), a member of the TRIM family, plays an important role in apoptosis, autophagy and ubiquitination in human, and has been proven to play antiviral roles in different organisms. In this study, the TRIM21 gene of Micropterus salmoides (MsTRIM21) was cloned, and it encoded 376 amino acids, which showed 89.3% similarity with Micropterus dolomieu and 38.3% with homo sapiens. Bioinformatics analysis revealed MsTRIM21 contained four domains: C4HC3-type RING-variant (RINGv), coiled coil, PRY and SPRY...

ABCF1 is the most characterized member of the ABCF family in eukaryotes with proposed functions related to innate immunity in fibroblasts, macrophages, and epithelial cells. Currently, a mechanistic link between ABCF1 and immune responses in human airway epithelial cells (HAECs) remains to be clearly defined. The present study aimed at characterizing the function of ABCF1 in the context of nuclear factor nuclear factor κB (NF-κB) mediated pro-inflammatory responses in an immortalized human airway epithelial cell line, HBEC-6KT...

The immunotherapy efficiency of stimulator of interferon genes (STING)-activatable drugs (e.g., 7-ethyl-10-hydroxycamptothecin, SN38) is limited by their non-specificity to tumor cells and the slow excretion of the DNA-containing exosomes from the treated cancer cells. The efficacy of tumor ferroptosis therapy is always limited by the elimination of lipid peroxides (LPO) by the pathways of glutathione peroxidase 4 (GPX4), dihydroorotate dehydrogenase (DHODH) and ferroptosis suppressor protein 1(FSP1). To solve these problems, in this study, we developed a STING pathway-activatable contrast agent (i...

Suppression of excessive inflammatory responses improves the survival of patients with sepsis. We previously illustrated the anti-inflammatory effects of fucoxanthin (FX), a natural carotenoid isolated from brown algae; nevertheless, the underlying mechanism remains unknown. In this study, we examine the mechanism of the action of FX by targeting interferon regulatory factor 3 (IRF3) to inhibit inflammatory response. We observed that FX regulated innate immunity by inhibiting IRF3 phosphorylation in vitro ...

Mesenchymal stem cells (MSCs) comprise a primitive cell population and reside in various tissues and organs. These cells exhibit immunomodulatory activity and are effective in treating respiratory viral infections. The activation of type I and III interferons, which protect cells against viral infections, can be induced after pattern recognition receptors (PRRs) recognize viral nucleic acid species. Although certain viruses can upregulate IFN-β expression in MSCs, the underlying mechanisms and responsiveness to different IFNs are unclear...

Probiotics are effective to treat or prevent gastrointestinal infections, and microalgae have demonstrated important health-promoting effects and in some cases function as prebiotics. In this regard, the anti-rotavirus effect of Bifidobacterium longum and Chlorella sorokiniana by reducing viral infectivity is well known. However, their effect on immune response against rotavirus has not yet been investigated. Therefore, the aim of this study was to determine the role of Bifidobacterium longum and/or Chlorella sorokiniana in influencing an IFN type I-mediated antiviral response in rotavirus-infected cells...