scholarly journals Why Females Do Better: The X Chromosomal TLR7 Gene-Dose Effect in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna E. Spiering ◽  
Teun J. de Vries
Keyword(s):  
Pattern Recognition ◽  
Viral Infections ◽  
Pattern Recognition Receptors ◽  
Dose Effect ◽  
Toll Like Receptor ◽  
Novel Studies ◽  
Gene Dose ◽  
Male Sex ◽  
Tlr7 Stimulation

A male sex bias has emerged in the COVID-19 pandemic, fitting to the sex-biased pattern in other viral infections. Males are 2.84 times more often admitted to the ICU and mortality is 1.39 times higher as a result of COVID-19. Various factors play a role in this, and novel studies suggest that the gene-dose of Toll-Like Receptor (TLR) 7 could contribute to the sex-skewed severity. TLR7 is one of the crucial pattern recognition receptors for SARS-CoV-2 ssRNA and the gene-dose effect is caused by X chromosome inactivation (XCI) escape. Female immune cells with TLR7 XCI escape have biallelic TLR7 expression and produce more type 1 interferon (IFN) upon TLR7 stimulation. In COVID-19, TLR7 in plasmacytoid dendritic cells is one of the pattern recognition receptors responsible for IFN production and a delayed IFN response has been associated with immunopathogenesis and mortality. Here, we provide a hypothesis that females may be protected to some extend against severe COVID-19, due to the biallelic TLR7 expression, allowing them to mount a stronger and more protective IFN response early after infection. Studies exploring COVID-19 treatment via the TLR7-mediated IFN pathway should consider this sex difference. Various factors such as age, sex hormones and escape modulation remain to be investigated concerning the TLR7 gene-dose effect.

scholarly journals Mitochondria, pattern recognition receptors and autophagy under physiological and pathological conditions, including viral infections

2021 ◽  
Author(s):  
Paulina Niedźwiedzka-Rystwej ◽  
Dominika Bębnowska ◽  
Roman Kołacz ◽  
Wiesław Deptuła
Keyword(s):  
Pattern Recognition ◽  
Viral Infections ◽  
Apoptotic Cell ◽  
Pattern Recognition Receptors ◽  
The Body ◽  
The Other ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Other Hand

Research on the health of mammals invariably shows how dynamic immunology is and how the role of many elements and immune processes of the macroorganism, developed in the process of evolution in protecting against threats, including infections, is changing. Among these elements conditioning the homeostasis of the macroorganism are mitochondria, PRR receptors (pattern recognition receptors) and the phenomenon of autophagy. In the context of physiological and pathological states in the body, mitochondria perform various functions. The primary function of these organelles is to produce energy in the cell, but on the other hand, they are heavily involved in various cellular processes, including ROS production and calcium homeostasis. They are largely involved in the activation of immune mechanisms during infectious and non-infectious conditions through mtDNA and the mitochondrial MAVS protein. Mitochondrial involvement has been also determined in PRR-related mechanisms as mtDNA has the ability to directly stimulate TLRs. On the other hand, mitochondria are also associated with apoptotic cell death and autophagy.

Pattern recognition receptor-mediated innate immune responses in seminal vesicle epithelial cell and their impacts on cellular function†

2019 ◽  
Vol 101 (4) ◽  
pp. 733-747 ◽  
Author(s):  
Maolei Gong ◽  
Fei Wang ◽  
Weihua Liu ◽  
Ran Chen ◽  
Han Wu ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Pattern Recognition Receptors ◽  
Seminal Vesicles ◽  
Pattern Recognition Receptor ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Recognition Receptor

Abstract The seminal vesicles can be infected by microorganisms, thereby resulting in vesiculitis and impairment in male fertility. Innate immune responses in seminal vesicles cells to microbial infections, which facilitate vesiculitis, have yet to be investigated. The present study aims to elucidate pattern recognition receptor–mediated innate immune responses in seminal vesicles epithelial cells. Various pattern recognition receptors, including Toll-like receptor 3, Toll-like receptor 4, cytosolic ribonucleic acid, and deoxyribonucleic acid sensors, are abundantly expressed in seminal vesicles epithelial cells. These pattern recognition receptors can recognize their respective ligands, thus activating nuclear factor kappa B and interferon regulatory factor 3. The pattern recognition receptor signaling induces expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha (Tnfa) and interleukin 6 (Il6), chemokines monocyte chemoattractant protein-1 (Mcp1) and C–X–C motif chemokine 10 (Cxcl10), and type 1 interferons Ifna and Ifnb. Moreover, pattern recognition receptor-mediated innate immune responses up-regulated the expression of microsomal prostaglandin E synthase and cyclooxygenase 2, but they down-regulated semenogelin-1 expression. These results provide novel insights into the mechanism underlying vesiculitis and its impact on the functions of the seminal vesicles.

scholarly journals RNase L amplifies Interferon signaling by inducing PKR-mediated antiviral stress granules

2020 ◽  
Author(s):  
Praveen Manivannan ◽  
Mohammad Adnan Siddiqui ◽  
Krishnamurthy Malathi
Keyword(s):  
Pattern Recognition ◽  
Virus Infection ◽  
Viral Infections ◽  
Stress Granules ◽  
Antiviral Response ◽  
Pattern Recognition Receptors ◽  
Stress Granule ◽  
Rna Cleavage ◽  
Rnase L ◽  
Rna Ligands

ABSTRACTVirus infection leads to activation of the interferon-induced endoribonuclease, RNase L, which results in degradation of viral and cellular RNAs. Both cellular and viral RNA cleavage products of RNase L bind pattern recognition receptors (PRR) like Retinoic acid-inducible I (Rig-I) and or melanoma differentiation-associated protein 5 (MDA5) to further amplify interferon (IFN) production and antiviral response. Although much is known about the mechanics of ligand binding and PRR activation, how the cells coordinate RNA sensing to signaling response and interferon production remains unclear. We show that RNA cleavage products of RNase L activity induce formation of antiviral stress granule (avSG) by regulating activation of double-stranded RNA (dsRNA)-dependent protein kinase R (PKR), and recruit antiviral proteins Rig-I, PKR, OAS and RNase L to avSG. Biochemical analysis of purified avSG showed interaction of key stress granule protein, G3BP1, with only PKR and Rig-I and not with OAS or RNase L. AvSG assembly during RNase L activation is required for IRF3-mediated IFN production and not IFN signaling or proinflammatory cytokine induction. Consequently, cells lacking avSG formation or RNase L signaling produced less IFN and showed higher susceptibility during Sendai virus infection demonstrating the importance of avSG in RNase L-mediated host defense. During viral infection, we propose a role for RNase L-cleaved RNAs in inducing avSG containing antiviral proteins to provide a platform for efficient interaction of RNA ligands with pattern recognition receptors to enhance IFN production to effectively mount antiviral response.IMPORTANCEDouble-stranded RNAs produced during viral infections serve as pathogen associated molecular patterns (PAMPs) and bind pattern recognition receptors to stimulate IFN production. RNase L is an IFN-regulated endoribonuclease that is activated in virus-infected cells and cleaves single-stranded viral and cellular RNAs. The RNase L-cleaved dsRNAs signal to Rig-like helicases to amplify IFN production. This study identifies a novel role of antiviral stress granules induced by RNase L as an antiviral signaling hub to coordinate the RNA ligands with cognate receptors to mount effective host response during viral infections.

scholarly journals RNase L Amplifies Interferon Signaling by Inducing Protein Kinase R-Mediated Antiviral Stress Granules

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Praveen Manivannan ◽  
Mohammad Adnan Siddiqui ◽  
Krishnamurthy Malathi
Keyword(s):  
Pattern Recognition ◽  
Protein Kinase ◽  
Virus Infection ◽  
Viral Infections ◽  
Stress Granules ◽  
Pattern Recognition Receptors ◽  
Rna Cleavage ◽  
Rnase L ◽  
Protein Kinase R ◽  
Rna Ligands

ABSTRACT Virus infection leads to activation of the interferon (IFN)-induced endoribonuclease RNase L, which results in degradation of viral and cellular RNAs. Both cellular and viral RNA cleavage products of RNase L bind pattern recognition receptors (PRRs), like retinoic acid-inducible I (Rig-I) and melanoma differentiation-associated protein 5 (MDA5), to further amplify IFN production and antiviral response. Although much is known about the mechanics of ligand binding and PRR activation, how cells coordinate RNA sensing with signaling response and interferon production remains unclear. We show that RNA cleavage products of RNase L activity induce the formation of antiviral stress granules (avSGs) by regulating activation of double-stranded RNA (dsRNA)-dependent protein kinase R (PKR) and recruit the antiviral proteins Rig-I, PKR, OAS, and RNase L to avSGs. Biochemical analysis of purified avSGs showed interaction of a key stress granule protein, G3BP1, with only PKR and Rig-I and not with OAS or RNase L. AvSG assembly during RNase L activation is required for IRF3-mediated IFN production, but not IFN signaling or proinflammatory cytokine induction. Consequently, cells lacking avSG formation or RNase L signaling produced less IFN and showed higher susceptibility during Sendai virus infection, demonstrating the importance of avSGs in RNase L-mediated host defense. We propose a role during viral infection for RNase L-cleaved RNAs in inducing avSGs containing antiviral proteins to provide a platform for efficient interaction of RNA ligands with pattern recognition receptors to enhance IFN production to mount an effective antiviral response. IMPORTANCE Double-stranded RNAs produced during viral infections serve as pathogen-associated molecular patterns (PAMPs) and bind pattern recognition receptors to stimulate IFN production. RNase L is an IFN-regulated endoribonuclease that is activated in virus-infected cells and cleaves single-stranded viral and cellular RNAs. The RNase L-cleaved dsRNAs signal to Rig-like helicases to amplify IFN production. This study identifies a novel role of antiviral stress granules induced by RNase L as an antiviral signaling hub to coordinate the RNA ligands with cognate receptors to mount an effective host response during viral infections.

scholarly journals Expression and regulation of the pattern recognition receptors Toll-like receptor-2 and Toll-like receptor-4 in the human placenta

Immunology ◽  
2002 ◽  
Vol 107 (1) ◽  
pp. 145-151 ◽  
Author(s):  
Ulrika Holmlund ◽  
Gvido Cebers ◽  
Agneta R. Dahlfors ◽  
Bengt Sandstedt ◽  
Katarina Bremme ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Human Placenta ◽  
Pattern Recognition Receptors ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Toll Like Receptor 2

scholarly journals Nucleotide Oligomerization Domain 2 (Nod2) Is Not Involved in the Pattern Recognition of Candida albicans

2006 ◽  
Vol 13 (3) ◽  
pp. 423-425 ◽  
Author(s):  
Chantal A. A. van der Graaf ◽  
Mihai G. Netea ◽  
Barbara Franke ◽  
Stephen E. Girardin ◽  
Jos W. M. van der Meer ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Candida Albicans ◽  
Cytokine Production ◽  
Nucleotide Binding ◽  
Pattern Recognition Receptors ◽  
Toll Like Receptor ◽  
Nucleotide Oligomerization ◽  
Toll Like Receptor 2 ◽  
Nucleotide Oligomerization Domain ◽  
Oligomerization Domain

ABSTRACT Nucleotide-binding oligomerization domain 2 (Nod2) pathways are known to interact with Toll-like receptor 2 (TLR2) and TLR4, which are pattern recognition receptors for Candida albicans. We observed that the prevalence of Nod2 polymorphisms was not increased in patients with Candida infections. Candida-induced cytokine production in individuals with Nod2 polymorphisms was unaffected. We conclude that Nod2 is unlikely to play an important role in the recognition of Candida albicans.

scholarly journals Molecular Mechanisms of the Toll-Like Receptor, STING, MAVS, Inflammasome, and Interferon Pathways

mSystems ◽  
2021 ◽  
Vol 6 (3) ◽  
Author(s):  
Nathan P. Manes ◽  
Aleksandra Nita-Lazar
Keyword(s):  
Pattern Recognition ◽  
Molecular Interaction ◽  
Molecular Mechanisms ◽  
Pattern Recognition Receptors ◽  
Toll Like Receptor ◽  
Front Line ◽  
Pathway Models

Pattern recognition receptors (PRRs) form the front line of defense against pathogens. Many of the molecular mechanisms that facilitate PRR signaling have been characterized in detail, which is critical for the development of accurate PRR pathway models at the molecular interaction level.

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