scholarly journals The Interplay between Human Cytomegalovirus and Pathogen Recognition Receptor Signaling

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 514 ◽  
Author(s):  
Mariana Marques ◽  
Ana Ferreira ◽  
Daniela Ribeiro
Keyword(s):  
Human Cytomegalovirus ◽  
Signaling Cascades ◽  
Interferon Stimulated Genes ◽  
Cellular Antiviral Response ◽  
Membrane Bound ◽  
The Many ◽  
Viral Components ◽  
Pathogen Recognition Receptor ◽  
Recognition Receptor ◽  
Pro Inflammatory Cytokines

The cellular antiviral innate immune response is triggered upon recognition of specific viral components by a set of the host’s cytoplasmic or membrane-bound receptors. This interaction induces specific signaling cascades that culminate with the production of interferons and the expression of interferon-stimulated genes and pro-inflammatory cytokines that act as antiviral factors, suppressing viral replication and restricting infection. Here, we review and discuss the different mechanisms by which each of these receptors is able to recognize and signal infection by the human cytomegalovirus (HCMV), an important human pathogen mainly associated with severe brain defects in newborns and disabilities in immunocompromised individuals. We further present and discuss the many sophisticated strategies developed by HCMV to evade these different signaling mechanisms and counteract the cellular antiviral response, in order to support cell viability and sustain its slow replication cycle.

scholarly journals Proinflammatory Soluble Interleukin-15 Receptor Alpha Is Increased in Rheumatoid Arthritis

Arthritis ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Ana Cecilia Machado Diaz ◽  
Araceli Chico Capote ◽  
Celia Aurora Arrieta Aguero ◽  
Yunier Rodríguez Alvarez ◽  
Diana García del Barco Herrera ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Reverse Signaling ◽  
Synovial Fluids ◽  
Inflammatory Processes ◽  
Membrane Bound ◽  
Interleukin 15 ◽  
Interleukin 15 Receptor Alpha ◽  
Pro Inflammatory Cytokines

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease in which many cytokines have been implicated. In particular, IL-15 is a cytokine involved in the inflammatory processes and bone loss. The aim of this study was to investigate the existence in synovial fluid of soluble IL-15Rα, a private receptor subunit for IL-15 which may act as an enhancer of IL-15-induced proinflammatory cytokines. Soluble IL-15Rα was quantified by a newly developed enzyme-linked immunosorbent assay (ELISA) in samples of synovial fluid from patients with RA and osteoarthritis (OA). The levels of IL-15Rα were significantly increased in RA patients compared to OA patients. Also, we studied the presence of membrane-bound IL-15 in cells from synovial fluids, another element necessary to induce pro-inflammatory cytokines through reverse signaling. Interestingly, we found high levels of IL-6 related to high levels of IL-15Rα in RA but not in OA. Thus, our results evidenced presence of IL-15Rα in synovial fluids and suggested that its pro-inflammatory effect could be related to induction of IL-6.

scholarly journals Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state

2019 ◽  
Vol 116 (37) ◽  
pp. 18619-18628 ◽  
Author(s):  
Jaewon Song ◽  
Sanghyun Lee ◽  
Dong-Yeon Cho ◽  
Sungwon Lee ◽  
Hyewon Kim ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Rna Processing ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Transcriptome Profiling ◽  
Loss Of Function ◽  
Antiviral Genes ◽  
Cellular Antiviral Response ◽  
Infected Cells

RNA represents a pivotal component of host–pathogen interactions. Human cytomegalovirus (HCMV) infection causes extensive alteration in host RNA metabolism, but the functional relationship between the virus and cellular RNA processing remains largely unknown. Through loss-of-function screening, we show that HCMV requires multiple RNA-processing machineries for efficient viral lytic production. In particular, the cellular RNA-binding protein Roquin, whose expression is actively stimulated by HCMV, plays an essential role in inhibiting the innate immune response. Transcriptome profiling revealed Roquin-dependent global down-regulation of proinflammatory cytokines and antiviral genes in HCMV-infected cells. Furthermore, using cross-linking immunoprecipitation (CLIP)-sequencing (seq), we identified IFN regulatory factor 1 (IRF1), a master transcriptional activator of immune responses, as a Roquin target gene. Roquin reduces IRF1 expression by directly binding to its mRNA, thereby enabling suppression of a variety of antiviral genes. This study demonstrates how HCMV exploits host RNA-binding protein to prevent a cellular antiviral response and offers mechanistic insight into the potential development of CMV therapeutics.

scholarly journals Hsa-miR-99b/let-7e/miR-125a Cluster Regulates Pathogen Recognition Receptor-Stimulated Suppressive Antigen-Presenting Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Dagmar Hildebrand ◽  
Mariel-Esther Eberle ◽  
Sabine Marie Wölfle ◽  
Franziska Egler ◽  
Delal Sahin ◽  
...  
Keyword(s):  
Antigen Presenting Cells ◽  
Pathogen Recognition ◽  
Antigen Presenting ◽  
Pathogen Recognition Receptor ◽  
Recognition Receptor

Detection of procoagulant imbalance

2017 ◽  
Vol 117 (05) ◽  
pp. 830-836 ◽  
Author(s):  
Armando Tripodi
Keyword(s):  
Protein C ◽  
Neutrophil Extracellular Traps ◽  
Relative Strength ◽  
Feedback Mechanisms ◽  
Turn On ◽  
Extracellular Traps ◽  
Increased Risk ◽  
The Many ◽  
Clinical Conditions ◽  
Pro Inflammatory Cytokines

SummaryEach individual possesses his/her own endogenous-thrombin-potential (ETP) (i. e. the ability to generate thrombin) which depends on the relative strength of the pro- and anticoagulant drivers operating in plasma. This ability depends in turn on the clinical conditions in which the balance between the two drivers is variably affected. One of the major determinants of this balance is the factor (F)VIII-protein C(PC) axis and its effect can be conveniently explored by the thrombin generation procedures with results expressed as ETP ratio with/without thrombomodulin (TM) (ETP-TM ratio). Furthermore, owing to the many feedback mechanisms mediated by thrombin (e. g. activation of PC, FXI, FV, FVIII, platelets etc.) it is also possible that any perturbation of the balance between pro- and anticoagulants that may occur in plasma even outside the FVIII-PC axis could result in an increased ETPTM ratio and therefore may suggest a procoagulant imbalance. Indeed, other non-coagulation moieties (e. g. microparticles, neutrophil extracellular traps, pro-inflammatory cytokines and others) circulating in blood of patients with various clinical conditions may also contribute to the procoagulant imbalance even when FVIII and/or PC are apparently normal. It can be postulated that dual ETP measurements performed in the presence and absence of TM with results expressed as their ratio may be the candidate procedure to detect subtle procoagulant imbalance in many clinical conditions characterised by an increased risk of thromboembolism. This article aimed at reviewing the clinical conditions in which evidence for the value of the ETP-TM ratio has been provided.

scholarly journals The Many Roles of Galectin-3, a Multifaceted Molecule, in Innate Immune Responses against Pathogens

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Laura Díaz-Alvarez ◽  
Enrique Ortega
Keyword(s):  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Terminal Protein ◽  
Molecular Pattern ◽  
Evolutionarily Conserved ◽  
Carbohydrate Recognition Domains ◽  
Galectin 3 ◽  
The Many ◽  
Recognition Receptor

Galectins are a group of evolutionarily conserved proteins with the ability to bindβ-galactosides through characteristic carbohydrate-recognition domains (CRD). Galectin-3 is structurally unique among all galectins as it contains a C-terminal CRD linked to an N-terminal protein-binding domain, being the only chimeric galectin. Galectin-3 participates in many functions, both intra- and extracellularly. Among them, a prominent role for Galectin-3 in inflammation has been recognized. Galectin-3 has also been shown to directly bind to pathogens and to have various effects on the functions of the cells of the innate immune system. Thanks to these two properties, Galectin-3 participates in several ways in the innate immune response against invading pathogens. Galectin-3 has been proposed to function not only as a pattern-recognition receptor (PRR) but also as a danger-associated molecular pattern (DAMP). In this review, we analyze the various roles that have been assigned to Galectin-3, both as a PRR and as a DAMP, in the context of immune responses against pathogenic microorganisms.

scholarly journals The Many Faces of Human Leukocyte Antigen-G: Relevance to the Fate of Pregnancy

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Mette Dahl ◽  
Snezana Djurisic ◽  
Thomas Vauvert F. Hviid
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Future Research ◽  
Placental Development ◽  
Leukocyte Antigen ◽  
Polymorphic Genes ◽  
Membrane Bound ◽  
The Many ◽  
Human Leukocyte Antigen G

Pregnancy is an immunological paradox, where fetal antigens encoded by polymorphic genes inherited from the father do not provoke a maternal immune response. The fetus is not rejected as it would be theorized according to principles of tissue transplantation. A major contribution to fetal tolerance is the human leukocyte antigen (HLA)-G, a nonclassical HLA protein displaying limited polymorphism, restricted tissue distribution, and a unique alternative splice pattern. HLA-G is primarily expressed in placenta and plays multifaceted roles during pregnancy, both as a soluble and a membrane-bound molecule. Its immunomodulatory functions involve interactions with different immune cells and possibly regulation of cell migration during placental development. Recent findings include HLA-G contributions from the father and the fetus itself. Much effort has been put into clarifying the role of HLA-G during pregnancy and pregnancy complications, such as preeclampsia, recurrent spontaneous abortions, and subfertility or infertility. This review aims to clarify the multifunctional role of HLA-G in pregnancy-related disorders by focusing on genetic variation, differences in mRNA stability betweenHLA-Galleles, differences in HLA-G isoform expression, and possible differences in functional activity. Furthermore, we highlight important observations regardingHLA-Ggenetics and expression in preeclampsia that future research should address.

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