scholarly journals Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Nicholas Stoy
Keyword(s):  
Interleukin 1 ◽  
Interferon Regulatory Factor ◽  
Innate Immune ◽  
Cytokine Storm ◽  
Regulatory Factor ◽  
Microbial Infection ◽  
Severe Morbidity ◽  
Interferon Regulatory Factor 5 ◽  
Cytokines And Chemokines ◽  
Endosomal Membranes

Interleukin-1 receptor-associated kinase 4 (IRAK4) and interferon regulatory factor 5 (IRF5) lie sequentially on a signaling pathway activated by ligands of the IL-1 receptor and/or multiple TLRs located either on plasma or endosomal membranes. Activated IRF5, in conjunction with other synergistic transcription factors, notably NF-κB, is crucially required for the production of proinflammatory cytokines in the innate immune response to microbial infection. The IRAK4-IRF5 axis could therefore have a major role in the induction of the signature cytokines and chemokines of the hyperinflammatory state associated with severe morbidity and mortality in COVID-19. Here a case is made for considering IRAK4 or IRF5 inhibitors as potential therapies for the “cytokine storm” of COVID-19.

scholarly journals O-GlcNAc transferase promotes influenza A virus–induced cytokine storm by targeting interferon regulatory factor–5

2020 ◽  
Vol 6 (16) ◽  
pp. eaaz7086 ◽  
Author(s):  
Qiming Wang ◽  
Peining Fang ◽  
Rui He ◽  
Mengqi Li ◽  
Haisheng Yu ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Cytokine Production ◽  
Interferon Regulatory Factor ◽  
Clinical Samples ◽  
Cytokine Storm ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5 ◽  
Key Enzyme ◽  
Glcnac Transferase

In this study, we demonstrated an essential function of the hexosamine biosynthesis pathway (HBP)–associated O-linked β-N-acetylglucosamine (O-GlcNAc) signaling in influenza A virus (IAV)–induced cytokine storm. O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, mediated IAV-induced cytokine production. Upon investigating the mechanisms driving this event, we determined that IAV induced OGT to bind to interferon regulatory factor–5 (IRF5), leading to O-GlcNAcylation of IRF5 on serine-430. O-GlcNAcylation of IRF5 is required for K63-linked ubiquitination of IRF5 and subsequent cytokine production. Analysis of clinical samples revealed that IRF5 is O-GlcNAcylated, and higher levels of proinflammatory cytokines correlated with higher levels of blood glucose in IAV-infected patients. We identified a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates IRF5 function during IAV infection, highlighting the importance of glucose metabolism in IAV-induced cytokine storm.

scholarly journals Molecular Cloning, Expression and Functional Analysis of Interferon Regulatory Factor 5 (IRF 5) in Malabar Grouper (Epinephelus Malabaricus)

2017 ◽  
Author(s):  
Thirunavukkarasu Periyasamy ◽  
Ming-Wei Lu
Keyword(s):  
Immune Responses ◽  
Sequence Similarity ◽  
Interferon Regulatory Factor ◽  
Innate Immune ◽  
Regulatory Factor ◽  
Transcriptional Responses ◽  
Oplegnathus Fasciatus ◽  
Interferon Regulatory Factor 5 ◽  
Wide Range ◽  
Epinephelus Malabaricus

Interferon regulatory factor 5 (IRF5) is known to be involved in the innate immune response and pro-inflammatory cytokines. However, the roles of IRF5 in immune responses in Malabar grouper (Epinephelus malabaricus) have not been extensively explored. In this study, IRF5 gene was identified and characterized from M. grouper. The full-length IRF5 cDNA consisted of a 5’ terminal untranslated region (5’-UTR) of 289 bp and a 3’-UTR of 542 bp, an open reading frame (ORF) of 1500 bp encoding a polypeptide of 499 amino acids with a predicted molecular mass of 56.28 kDa and isoelectric point (pI) of 5.2. The putative MgIRF5 protein consists of four important conserved domains: a helix DNA-binding domain (DBD) at the N-terminus, a middle region, an IRF association domain (IAD) and a virus activated domain (VAD) at the C-terminus. Sequence alignment and phylogenetic analysis showed that highest sequence similarity of IRF5 was observed between the IRF5 genes from Oplegnathus fasciatus and Miichthys miiuy. The mRNA transcripts of IRF5 were detected in a wide range of tissues types from healthy M. grouper with highest expression in muscle, liver and skin. After treatment with poly (I: C), it was significantly up-regulated in spleen and liver tissues. When infected with NNV, the expression level of MgIRF5 was up-regulated in spleen and head kidney and their transcriptional responses to IRF5 increased in the grouper kidney cells. This approach suggests that MgIRF5 is important in the underlying mechanism of the innate immune responses against antiviral response.

scholarly journals Association of a haplotype in the promoter region of the interferon regulatory factor 5 gene with rheumatoid arthritis

2007 ◽  
Vol 56 (7) ◽  
pp. 2202-2210 ◽  
Author(s):  
Snaevar Sigurdsson ◽  
Leonid Padyukov ◽  
Fina A. S. Kurreeman ◽  
Ulrika Liljedahl ◽  
Ann-Christin Wiman ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Promoter Region ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5

scholarly journals SARS CoV-2 Might Exploit Cells of the Innate Immune System to Induce the Novel Acute Immune Dysrhythmic Syndrome (n-AIDS) and Para COVID-19 Syndrome.

2021 ◽  
Author(s):  
Mina Kelleni
Keyword(s):  
Immune Response ◽  
Innate Immune System ◽  
Langerhans Cells ◽  
Interesting Case ◽  
Innate Immune ◽  
Delayed Type Hypersensitivity ◽  
The Novel ◽  
Cytokine Storm ◽  
Humoral Immune ◽  
Cytokines And Chemokines

In this manuscript, we combine our insights towards COVID-19 to present a hypothesis that might explain its pathogenesis and complications while presenting an interesting case report of post COVID-19 allergic cell mediated (dysregulated) delayed type hypersensitivity. Moreover, we confirm our call to reclassify it as novel acute immune dysrhythmic syndrome (n-AIDS) to include both cytokine storm and we suggest to describe post or long COVID and other autoimmune complications as para COVID-19 syndrome. We suggest that SARS CoV-2 might exploit monocytes, macrophages and tissue resident macrophages including skin Langerhans cells to induce dysregulated cellular and humoral immune response through known and yet to be discovered cytokines and chemokines to ultimately induce the cytokine storm and/or autoimmune responses.

Associations between interferon regulatory factor 5 polymorphisms and rheumatoid arthritis: a meta-analysis

2012 ◽  
Vol 40 (2) ◽  
pp. 1791-1799 ◽  
Author(s):  
Young Ho Lee ◽  
Sang-Cheol Bae ◽  
Sung Jae Choi ◽  
Jong Dae Ji ◽  
Gwan Gyu Song
Keyword(s):  
Rheumatoid Arthritis ◽  
Meta Analysis ◽  
Interferon Regulatory Factor ◽  
Regulatory Factor ◽  
Interferon Regulatory Factor 5

scholarly journals Interferon Regulatory Factor 5 Mediates Lipopolysaccharide-Induced Neuroinflammation

2020 ◽  
Vol 11 ◽  
Author(s):  
Ziqi Fan ◽  
Shuai Zhao ◽  
Yueli Zhu ◽  
Zheyu Li ◽  
Zhirong Liu ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Interferon Regulatory Factor ◽  
Microglial Cells ◽  
Regulatory Factor ◽  
Down Regulation ◽  
Interferon Regulatory Factor 5 ◽  
Bv2 Microglial Cells ◽  
Lps Treatment ◽  
Pro Inflammatory Cytokines

BackgroundActivated microglia play a vital role in neuroinflammation in the central nervous system (CNS), which is associated with the pathogenesis and the progression of neurological diseases. Interferon regulatory factor 5 (IRF5) has been well established participating in inflammatory responses and is highly expressed in M1 macrophage in the periphery, the role of which in the CNS remains elusive.MethodsLipopolysaccharide (LPS) was employed to induce neuroinflammation. Down-regulation of IRF5 in C57/BL6 mice and BV2 microglial cells were achieved by IRF5 siRNA transfection. The levels of pro-inflammatory cytokines were evaluated by ELISA and quantitative real-time PCR. The expression levels of IRF5 were examined by immunofluorescence and Western blot.ResultsLPS induced significantly elevated expression of IRF5 in mouse brain, which co-localized with CD11b-positive microglia. Down-regulation of IRF5 quenched the pro-inflammatory responses. The levels of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 were up-regulated at 4 h after LPS treatment, which were significantly down-regulated with the knockdown of IRF5. LPS-induced pro-inflammatory responses were transient, which were comparable to control group at 24 h after LPS treatment. However, LPS did not up-regulate the expression of IRF5 in BV2 microglial cells, indicating that LPS-induced inflammation in BV2 cells does not involve IRF5 signaling.ConclusionsIRF5 mediates the inflammatory responses in the CNS, which might serve as a therapeutic target for CNS inflammatory diseases. LPS-induced inflammation does not involve IRF5 signaling in BV2 microglia.

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