scholarly journals Bmp8a Is a Novel Player in Regulation of Antiviral Immunity

2020 ◽  
Author(s):  
Shenjie Zhong ◽  
Haoyi Li ◽  
Yun-Sheng Wang ◽  
Ying Wang ◽  
Guangdong Ji ◽  
...  
Keyword(s):  
Virus Infection ◽  
Immune Responses ◽  
Mapk Pathway ◽  
Antiviral Immunity ◽  
Vital Role ◽  
Type I ◽  
Type I Ifns ◽  
Morphogenetic Protein ◽  
First Time

AbstractBone morphogenetic protein (BMP) is a kind of classical multi-functional growth factor that plays a vital role in the formation and maintenance of bone, cartilage, muscle, blood vessels, and the regulation of energy balance. Whether BMP plays a role in antiviral immunity is unknown. Here we demonstrate that Bmp8a is a newly-identified positive regulator for antiviral immune responses. The bmp8a−/− zebrafish, when infected with the viruses of GCRV, SVCV or TSVDV, show significantly reduced antiviral immunity, increased viral load and morbidity. We also show for the first time that Bmp8a interacts with Alk6a, which promotes the phosphorylation of Tbk1 and Irf3 through p38 MAPK pathway, and induces the production of type I IFNs in response to virus infection. Upon virus infection, bmp8a expression is activated through the binding of Stat1a/Stat1b to the GAS motifs in bmp8a promoter region, enlarging the antiviral innate immune signal. Our study uncovers a previously unrecognized role of Bmp8a in regulation of antiviral immune responses and provides a new target for controlling viral infection.

scholarly journals Bmp8a is an essential positive regulator of antiviral immunity in zebrafish

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Shenjie Zhong ◽  
Haoyi Li ◽  
Yun-Sheng Wang ◽  
Ying Wang ◽  
Guangdong Ji ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Infection ◽  
Mapk Pathway ◽  
Antiviral Immunity ◽  
Vital Role ◽  
Type I Interferons ◽  
Type I ◽  
Positive Regulator ◽  
Morphogenetic Protein

AbstractBone morphogenetic protein (BMP) is a kind of classical multi-functional growth factor that plays a vital role in the formation and maintenance of bone, cartilage, muscle, blood vessels, and the regulation of adipogenesis and thermogenesis. However, understanding of the role of BMPs in antiviral immunity is still limited. Here we demonstrate that Bmp8a is a newly-identified positive regulator for antiviral immune responses. The bmp8a−/− zebrafish, when infected with viruses, show reduced antiviral immunity and increased viral load and mortality. We also show for the first time that Bmp8a interacts with Alk6a, which promotes the phosphorylation of Tbk1 and Irf3 through p38 MAPK pathway, and induces the production of type I interferons (IFNs) in response to viral infection. Our study uncovers a previously unrecognized role of Bmp8a in regulation of antiviral immune responses and provides a target for controlling viral infection.

scholarly journals Type I Interferons Mediate the Innate Cytokine Response to Recombinant Fowlpox Virus but Not the Induction of Plasmacytoid Dendritic Cell-Dependent Adaptive Immunity

2010 ◽  
Vol 84 (13) ◽  
pp. 6549-6563 ◽  
Author(s):  
Erin L. Lousberg ◽  
Cara K. Fraser ◽  
Michael G. Tovey ◽  
Kerrilyn R. Diener ◽  
John D. Hayball
Keyword(s):  
Immune Responses ◽  
Plasmacytoid Dendritic Cell ◽  
Type I Interferons ◽  
Interleukin 12 ◽  
Type I ◽  
Adaptive Immune Responses ◽  
Fowlpox Virus ◽  
Adaptive Immune ◽  
Type I Ifns

ABSTRACT Type I interferons (IFNs) are considered to be important mediators of innate immunity due to their inherent antiviral activity, ability to drive the transcription of a number of genes involved in viral clearance, and their role in the initiation of innate and adaptive immune responses. Due to the central role of type I IFNs, we sought to determine their importance in the generation of immunity to a recombinant vaccine vector fowlpox virus (FPV). In analyzing the role of type I IFNs in immunity to FPV, we show that they are critical to the secretion of a number of innate and proinflammatory cytokines, including type I IFNs themselves as well as interleukin-12 (IL-12), tumor necrosis factor-alpha (TNF-α), IL-6, and IL-1β, and that deficiency leads to enhanced virus-mediated antigen expression. Interestingly, however, type I IFNs were not required for adaptive immune responses to recombinant FPV even though plasmacytoid dendritic cells (pDCs), the primary producers of type I IFNs, have been shown to be requisite for this to occur. Furthermore, we provide evidence that the importance of pDCs may lie in their ability to capture and present virally derived antigen to T cells rather than in their capacity as professional type I IFN-producing cells.

scholarly journals Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons

2020 ◽  
Author(s):  
Daisy X. Ji ◽  
Kristen C. Witt ◽  
Dmitri I. Kotov ◽  
Shally R. Margolis ◽  
Alexander Louie ◽  
...  
Keyword(s):  
Immune Responses ◽  
Legionella Pneumophila ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Transcriptional Regulator ◽  
Type I Interferons ◽  
Type I ◽  
Viral Immunity ◽  
Type I Ifns

AbstractType I interferons (IFNs) are essential for anti-viral immunity, but often impair protective immune responses during bacterial infections. How type I IFNs are strongly induced during viral infections, and yet are appropriately restrained during bacterial infections, remains poorly understood. The Super susceptibility to tuberculosis 1 (Sst1) locus in mice confers resistance to many bacterial infections. Here we provide evidence that Sp140 is a gene encoded within the Sst1 locus that functions to repress the expression of type I IFNs during bacterial infections. We generated Sp140−/− mice and find they are susceptible to infection by diverse bacteria, including Listeria monocytogenes, Legionella pneumophila, and Mycobacterium tuberculosis. Susceptibility of Sp140−/− mice to bacterial infection was rescued by crosses to mice lacking the type I IFN receptor (Ifnar−/−). Our results implicate Sp140 as an important repressor of type I IFNs that is essential for resistance to bacterial infections.

scholarly journals Abrogation of the Interferon Response Promotes More Efficient Human Cytomegalovirus Replication

2014 ◽  
Vol 89 (2) ◽  
pp. 1479-1483 ◽  
Author(s):  
Brian P. McSharry ◽  
Simone K. Forbes ◽  
Selmir Avdic ◽  
Richard E. Randall ◽  
Gavin W. G. Wilkinson ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Vital Role ◽  
Human Cells ◽  
Interferon Response ◽  
Type I ◽  
Type I Ifns ◽  
Hcmv Replication ◽  
Primary Human Cells

The effect of abrogating the interferon (IFN) response on human cytomegalovirus (HCMV) replication was investigated using primary human cells engineered to block either the production of or the response to type I IFNs. In IFN-deficient cells, HCMV produced larger plaques and spread and replicated more rapidly than in parental cells. These cells demonstrate the vital role of IFNs in controlling HCMV replication and provide useful tools to investigate the IFN response to HCMV.

scholarly journals Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Wei Liu ◽  
Jing Li ◽  
Weinan Zheng ◽  
Yingli Shang ◽  
Zhendong Zhao ◽  
...  
Keyword(s):  
Virus Infection ◽  
Immune Responses ◽  
Ubiquitin Ligase ◽  
Sendai Virus ◽  
Rna Virus ◽  
Cyclophilin A ◽  
Type I Interferons ◽  
Type I ◽  
Recognition Receptor

RIG-I is a key cytosolic pattern recognition receptor that interacts with MAVS to induce type I interferons (IFNs) against RNA virus infection. In this study, we found that cyclophilin A (CypA), a peptidyl-prolyl cis/trans isomerase, functioned as a critical positive regulator of RIG-I-mediated antiviral immune responses. Deficiency of CypA impaired RIG-I-mediated type I IFN production and promoted viral replication in human cells and mice. Upon Sendai virus infection, CypA increased the interaction between RIG-I and its E3 ubiquitin ligase TRIM25, leading to enhanced TRIM25-mediated K63-linked ubiquitination of RIG-I that facilitated recruitment of RIG-I to MAVS. In addition, CypA and TRIM25 competitively interacted with MAVS, thereby inhibiting TRIM25-induced K48-linked ubiquitination of MAVS. Taken together, our findings reveal an essential role of CypA in boosting RIG-I-mediated antiviral immune responses by controlling the ubiquitination of RIG-I and MAVS.

scholarly journals Role of the Innate Immunity Signaling Pathway in the Pathogenesis of Sjögren’s Syndrome

2021 ◽  
Vol 22 (6) ◽  
pp. 3090
Author(s):  
Toshimasa Shimizu ◽  
Hideki Nakamura ◽  
Atsushi Kawakami
Keyword(s):  
Immune Responses ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Innate Immune ◽  
Type I ◽  
Type I Ifn ◽  
Adaptive Immune ◽  
Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of the salivary and lacrimal glands and extra-glandular lesions. Adaptive immune response including T- and B-cell activation contributes to the development of SS. However, its pathogenesis has not yet been elucidated. In addition, several patients with SS present with the type I interferon (IFN) signature, which is the upregulation of the IFN-stimulated genes induced by type I IFN. Thus, innate immune responses including type I IFN activity are associated with SS pathogenesis. Recent studies have revealed the presence of activation pattern recognition receptors (PRRs) including Toll-like receptors, RNA sensor retinoic acid-inducible gene I and melanoma differentiation-associated gene 5, and inflammasomes in infiltrating and epithelial cells of the salivary glands among patients with SS. In addition, the activation of PRRs via the downstream pathway such as the type I IFN signature and nuclear factor kappa B can directly cause organ inflammation, and it is correlated with the activation of adaptive immune responses. Therefore, this study assessed the role of the innate immune signal pathway in the development of inflammation and immune abnormalities in SS.

scholarly journals Role of Alternative Splicing in Regulating Host Response to Viral Infection

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1720
Author(s):  
Kuo-Chieh Liao ◽  
Mariano A. Garcia-Blanco
Keyword(s):  
Innate Immunity ◽  
Alternative Splicing ◽  
Immune Responses ◽  
Viral Infection ◽  
Rna Splicing ◽  
Type I ◽  
Host Immune Responses ◽  
Transcriptional Regulatory Mechanisms ◽  
Host Virus Interactions

The importance of transcriptional regulation of host genes in innate immunity against viral infection has been widely recognized. More recently, post-transcriptional regulatory mechanisms have gained appreciation as an additional and important layer of regulation to fine-tune host immune responses. Here, we review the functional significance of alternative splicing in innate immune responses to viral infection. We describe how several central components of the Type I and III interferon pathways encode spliced isoforms to regulate IFN activation and function. Additionally, the functional roles of splicing factors and modulators in antiviral immunity are discussed. Lastly, we discuss how cell death pathways are regulated by alternative splicing as well as the potential role of this regulation on host immunity and viral infection. Altogether, these studies highlight the importance of RNA splicing in regulating host–virus interactions and suggest a role in downregulating antiviral innate immunity; this may be critical to prevent pathological inflammation.

scholarly journals The Role of NKT Cells in Glioblastoma

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1641
Author(s):  
Emily E. S. Brettschneider ◽  
Masaki Terabe
Keyword(s):  
Immune Responses ◽  
Cell Activity ◽  
Nkt Cells ◽  
Type I ◽  
Type Ii ◽  
Central Nervous System Diseases ◽  
Nkt Cell ◽  
Lipid Antigens ◽  
Immunoregulatory Mechanisms

Glioblastoma is an aggressive and deadly cancer, but to date, immunotherapies have failed to make significant strides in improving prognoses for glioblastoma patients. One of the current challenges to developing immunological interventions for glioblastoma is our incomplete understanding of the numerous immunoregulatory mechanisms at play in the glioblastoma tumor microenvironment. We propose that Natural Killer T (NKT) cells, which are unconventional T lymphocytes that recognize lipid antigens presented by CD1d molecules, may play a key immunoregulatory role in glioblastoma. For example, evidence suggests that the activation of type I NKT cells can facilitate anti-glioblastoma immune responses. On the other hand, type II NKT cells are known to play an immunosuppressive role in other cancers, as well as to cross-regulate type I NKT cell activity, although their specific role in glioblastoma remains largely unclear. This review provides a summary of our current understanding of NKT cells in the immunoregulation of glioblastoma as well as highlights the involvement of NKT cells in other cancers and central nervous system diseases.

scholarly journals ICSBP-mediated immune protection against BCR-ABL–induced leukemia requires the CCL6 and CCL9 chemokines

Blood ◽  
2009 ◽  
Vol 113 (16) ◽  
pp. 3813-3820 ◽  
Author(s):  
Valentina Nardi ◽  
Olaia Naveiras ◽  
Mohammad Azam ◽  
George Q. Daley
Keyword(s):  
Murine Model ◽  
Consensus Sequence ◽  
Myelogenous Leukemia ◽  
Transformed Cells ◽  
Type I ◽  
Immune Protection ◽  
Immune Mechanism ◽  
Type I Ifns ◽  
New Strategies

Abstract Interferon (IFN) is effective at inducing complete remissions in patients with chronic myelogenous leukemia (CML), and evidence supports an immune mechanism. Here we show that the type I IFNs (alpha and beta) regulate expression of the IFN consensus sequence-binding protein (ICSBP) in BCR-ABL–transformed cells and as shown previously for ICSBP, induce a vaccine-like immunoprotective effect in a murine model of BCR-ABL–induced leukemia. We identify the chemokines CCL6 and CCL9 as genes prominently induced by the type I IFNs and ICSBP, and demonstrate that these immunomodulators are required for the immunoprotective effect of ICSBP expression. Insights into the role of these chemokines in the antileukemic response of IFNs suggest new strategies for immunotherapy of CML.

Role of the chaperone protein 14-3-3ε in the regulation of influenza A virus-activated beta interferon

2021 ◽  
Author(s):  
Ee-Hong Tam ◽  
Yen-Chin Liu ◽  
Chian-Huey Woung ◽  
Helene Minyi Liu ◽  
Guan-Hong Wu ◽  
...  
Keyword(s):  
Virus Infection ◽  
Influenza A Virus ◽  
Influenza A ◽  
Critical Role ◽  
Type I ◽  
Type I Ifn ◽  
Ns1 Protein ◽  
Chaperone Protein ◽  
Influenza A Virus Infection

The NS1 protein of the influenza A virus plays a critical role in regulating several biological processes in cells, including the type I interferon (IFN) response. We previously profiled the cellular factors that interact with the NS1 protein of influenza A virus and found that the NS1 protein interacts with proteins involved in RNA splicing/processing, cell cycle regulation, and protein targeting processes, including 14-3-3ε. Since 14-3-3ε plays an important role in RIG-I translocation to MAVS to activate type I IFN expression, the interaction of the NS1 and 14-3-3ε proteins may prevent the RIG-I-mediated IFN response. In this study, we confirmed that the 14-3-3ε protein interacts with the N-terminal domain of the NS1 protein and that the NS1 protein inhibits RIG-I-mediated IFN-β promoter activation in 14-3-3ε-overexpressing cells. In addition, our results showed that knocking down 14-3-3ε can reduce IFN-β expression elicited by influenza A virus and enhance viral replication. Furthermore, we found that threonine in the 49 th amino acid position of the NS1 protein plays a role in the interaction with 14-3-3ε. Influenza A virus expressing C-terminus-truncated NS1 with T49A mutation dramatically increases IFN-β mRNA in infected cells and causes slower replication than that of virus without the T-to-A mutation. Collectively, this study demonstrates that 14-3-3ε is involved in influenza A virus-initiated IFN-β expression and that the interaction of the NS1 protein and 14-3-3ε may be one of the mechanisms for inhibiting type I IFN activation during influenza A virus infection. IMPORTANCE Influenza A virus is an important human pathogen causing severe respiratory disease. The virus has evolved several strategies to dysregulate the innate immune response and facilitate its replication. We demonstrate that the NS1 protein of influenza A virus interacts with the cellular chaperone protein 14-3-3ε, which plays a critical role in RIG-I translocation that induces type I IFN expression, and that NS1 protein prevents RIG-I translocation to mitochondrial membrane. The interaction site for 14-3-3ε is the RNA-binding domain (RBD) of the NS1 protein. Therefore, this research elucidates a novel mechanism by which the NS1 RBD mediates IFN-β suppression to facilitate influenza A viral replication. Additionally, the findings reveal the antiviral role of 14-3-3ε during influenza A virus infection.

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