scholarly journals Cellular Responses to Cytosolic Double-stranded RNA–-The Role of the Inflammasome

2014 ◽  
Vol 6 ◽  
pp. III.S17839 ◽  
Author(s):  
Adi Idris
Keyword(s):  
Innate Immune System ◽  
Viral Infections ◽  
Cellular Responses ◽  
Specific Pattern ◽  
Innate Immune ◽  
Host Cells ◽  
Virus Infected Cell ◽  
Double Stranded Rna ◽  
Molecular Patterns

Sensing the presence of a pathogen is an evolutionarily ancient trait, especially for cells of the innate immune system. The innate immune response against pathogens, such as viruses, begins with recognition of pathogen-associated molecular patterns (PAMPs) by specific pattern-recognition receptors (PRRs). Cytosolic double-stranded RNA (dsRNA) is emerging as a critical PAMP in the detection of viral infections. This recognition results in the production of antiviral and proinflammatory cytokines and, often, the death of the virus-infected cell. This review focuses on the current developments in the role of inflammasomes in response to the presence of cytosolic dsRNA in host cells. More importantly, it highlights important unanswered questions that if addressed will help us better understand the ways in which host cells respond to viral infection, in particular RNA viruses.

scholarly journals Emerging Role of PYHIN Proteins as Antiviral Restriction Factors

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1464
Author(s):  
Matteo Bosso ◽  
Frank Kirchhoff
Keyword(s):  
Viral Infections ◽  
Specific Pattern ◽  
Immune Defense ◽  
Innate Immune ◽  
Cellular Proteins ◽  
Restriction Factors ◽  
First Line ◽  
Viral Pathogens ◽  
Molecular Patterns

Innate immune sensors and restriction factors are cellular proteins that synergize to build an effective first line of defense against viral infections. Innate sensors are usually constitutively expressed and capable of detecting pathogen-associated molecular patterns (PAMPs) via specific pattern recognition receptors (PRRs) to stimulate the immune response. Restriction factors are frequently upregulated by interferons (IFNs) and may inhibit viral pathogens at essentially any stage of their replication cycle. Members of the Pyrin and hematopoietic interferon-inducible nuclear (HIN) domain (PYHIN) family have initially been recognized as important sensors of foreign nucleic acids and activators of the inflammasome and the IFN response. Accumulating evidence shows, however, that at least three of the four members of the human PYHIN family restrict viral pathogens independently of viral sensing and innate immune activation. In this review, we provide an overview on the role of human PYHIN proteins in the innate antiviral immune defense and on viral countermeasures.

scholarly journals Role of Toll-Like Receptors in Activation of Porcine Alveolar Macrophages by Porcine Reproductive and Respiratory Syndrome Virus

2009 ◽  
Vol 16 (3) ◽  
pp. 360-365 ◽  
Author(s):  
Laura C. Miller ◽  
Kelly M. Lager ◽  
Marcus E. Kehrli
Keyword(s):  
Alveolar Macrophages ◽  
Viral Infections ◽  
Rna Virus ◽  
Innate Immune ◽  
Respiratory Syndrome Virus ◽  
Double Stranded Rna ◽  
Tlr4 Activation ◽  
Molecular Patterns ◽  
Rapid Activation

ABSTRACT Control of virus replication initially depends on rapid activation of the innate immune response. Toll-like receptor (TLR) ligands are potent inducers of innate immunity against viral infections. Porcine reproductive and respiratory syndrome virus (PRRSV), a positive-sense RNA virus, initiates infection in porcine alveolar macrophages (PAMs), elicits weak immune responses, and establishes a persistent infection. To understand the role of single-stranded RNA and double-stranded RNA (dsRNA) intermediates in eliciting host immunity, we sought to determine if TLRs, particularly those that respond to viral molecular patterns, are involved in PRRSV infection. Activation of TLR3 in PAMs with dsRNA increased gene expression for alpha interferon and suppressed PRRSV infectivity. In contrast, TLR4 activation by the treatment of PAMs with lipopolysaccharide did not influence PRRSV infectivity.

Role of Toll-like receptors in liver health and disease

2011 ◽  
Vol 121 (10) ◽  
pp. 415-426 ◽  
Author(s):  
Ruth Broering ◽  
Mengji Lu ◽  
Joerg F. Schlaak
Keyword(s):  
Immune System ◽  
Liver Disease ◽  
Innate Immune System ◽  
Innate Immune ◽  
Toll Like Receptors ◽  
Evolutionarily Conserved ◽  
Liver Health ◽  
Health And Disease ◽  
Molecular Patterns

TLRs (Toll-like receptors), as evolutionarily conserved germline-encoded pattern recognition receptors, have a crucial role in early host defence by recognizing so-called PAMPs (pathogen-associated molecular patterns) and may serve as an important link between innate and adaptive immunity. In the liver, TLRs play an important role in the wound healing and regeneration processes, but they are also involved in the pathogenesis and progression of various inflammatory liver diseases, including autoimmune liver disease, alcoholic liver disease, non-alcoholic steatohepatitis, fibrogenesis, and chronic HBV (hepatitis B virus) and HCV (hepatitis C virus) infection. Hepatitis viruses have developed different evading strategies to subvert the innate immune system. Thus recent studies have suggested that TLR-based therapies may represent a promising approach in the treatment in viral hepatitis. The present review focuses on the role of the local innate immune system, and TLRs in particular, in the liver.

scholarly journals Cathepsins: innate immune proteases that regulate viral entry into host cells

2018 ◽  
Vol 72 ◽  
pp. 253-263 ◽  
Author(s):  
Magdalena Bossowska-Nowicka ◽  
Felix N. Toka ◽  
Matylda Mielcarska ◽  
Lidia Szulc-Dąbrowska
Keyword(s):  
Viral Entry ◽  
Antigen Processing ◽  
Viral Infections ◽  
Innate Immune ◽  
Host Cells ◽  
Human Pathogens ◽  
Cellular Mechanisms ◽  
Cathepsin Proteases ◽  
Cell Adhesion And Migration

Cathepsins are group of endolysosomal proteases that regulate the mechanisms of innate and adaptive immunity, including cell adhesion and migration, antigen processing and presentation and resistance to several viral infections. Some cathepsins are required for Toll-like receptor (TLR)3, TLR7 and TLR9 cleavage and the formation of functional receptors that participate in sensing viral nucleic acids. Moreover, cathepsins directly stimulate or inhibit cytokine secretion involved in the regulation of antiviral innate immune response. Recent findings underline the important role of cathepsins in the entry of filoviruses, reoviruses, retroviruses and other types of viruses into the host cell. Many enveloped viruses require the presence of cathepsins for efficient fusion with membranes of infected cells, and the inhibition of their activity results in a significant reduction of virus replication. In addition, many viruses utilize conserved cellular mechanisms, such as endocytosis or low pH within the endosome, for efficient penetration into the cell interior, disassembly of viral capsid, and other stages of productive viral replication cycle. Therefore, a better understanding of the functional role of cathepsin proteases in the pathogenesis of viral infections should lead to the development of novel therapeutics for a variety of particularly dangerous human pathogens.

scholarly journals Toll-like receptors and damage-associated molecular patterns: novel links between inflammation and hypertension

2014 ◽  
Vol 306 (2) ◽  
pp. H184-H196 ◽  
Author(s):  
Cameron G. McCarthy ◽  
Styliani Goulopoulou ◽  
Camilla F. Wenceslau ◽  
Kathryn Spitler ◽  
Takayuki Matsumoto ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Cell Injury ◽  
Receptor Activation ◽  
Innate Immune ◽  
Immune System Activation ◽  
System Activation ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Low-grade systemic inflammation is a common manifestation of hypertension; however, the exact mechanisms that initiate this pathophysiological response, thereby contributing to further increases in blood pressure, are not well understood. Aberrant vascular inflammation and reactivity via activation of the innate immune system may be the first step in the pathogenesis of hypertension. One of the functions of the innate immune system is to recognize and respond to danger. Danger signals can arise from not only pathogenic stimuli but also endogenous molecules released following cell injury and/or death [damage-associated molecular patterns (DAMPs)]. In the short-term, activation of the innate immune system is beneficial in the vasculature by providing cytoprotective mechanisms and facilitating tissue repair following injury or infection. However, sustained or excessive immune system activation, such as in autoimmune diseases, may be deleterious and can lead to maladaptive, irreversible changes to vascular structure and function. An initial source of DAMPs that enter the circulation to activate the innate immune system could arise from modest elevations in peripheral vascular resistance. These stimuli could subsequently lead to ischemic- or pressure-induced events aggravating further cell injury and/or death, providing more DAMPs for innate immune system activation. This review will address and critically evaluate the current literature on the role of the innate immune system in hypertension pathogenesis. The role of Toll-like receptor activation on somatic cells of the vasculature in response to the release of DAMPs and the consequences of this activation on inflammation, vasoreactivity, and vascular remodeling will be specifically discussed.

scholarly journals For Better or for Worse: A Look Into Neutrophils in Traumatic Spinal Cord Injury

2021 ◽  
Vol 15 ◽  
Author(s):  
Sandra Zivkovic ◽  
Maryam Ayazi ◽  
Grace Hammel ◽  
Yi Ren
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Innate Immune System ◽  
Tissue Injury ◽  
Innate Immune ◽  
Traumatic Spinal Cord Injury ◽  
Injured Spinal Cord ◽  
Cord Injury ◽  
Molecular Patterns

Neutrophils are short-lived cells of the innate immune system and the first line of defense at the site of an infection and tissue injury. Pattern recognition receptors on neutrophils recognize pathogen-associated molecular patterns or danger-associated molecular patterns, which recruit them to the destined site. Neutrophils are professional phagocytes with efficient granular constituents that aid in the neutralization of pathogens. In addition to phagocytosis and degranulation, neutrophils are proficient in creating neutrophil extracellular traps (NETs) that immobilize pathogens to prevent their spread. Because of the cytotoxicity of the associated granular proteins within NETs, the microbes can be directly killed once immobilized by the NETs. The role of neutrophils in infection is well studied; however, there is less emphasis placed on the role of neutrophils in tissue injury, such as traumatic spinal cord injury. Upon the initial mechanical injury, the innate immune system is activated in response to the molecules produced by the resident cells of the injured spinal cord initiating the inflammatory cascade. This review provides an overview of the essential role of neutrophils and explores the contribution of neutrophils to the pathologic changes in the injured spinal cord.

scholarly journals Role of metabolism during viral infections, and crosstalk with the innate immune system

2016 ◽  
Vol 5 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Juan José González Plaza ◽  
Nataša Hulak ◽  
Galina Kausova ◽  
Zhaxybay Zhumadilov ◽  
Ainur Akilzhanova
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Viral Infections ◽  
Innate Immune

scholarly journals The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia

2021 ◽  
Vol 22 (3) ◽  
pp. 1271
Author(s):  
Laura Urwanisch ◽  
Michela Luciano ◽  
Jutta Horejs-Hoeck
Keyword(s):  
Nlrp3 Inflammasome ◽  
Innate Immune System ◽  
Inflammatory Cell ◽  
Current Knowledge ◽  
Innate Immune ◽  
Leukemic Cells ◽  
Different Types ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Chronic inflammation contributes to the development and progression of various tumors. Especially where the inflammation is mediated by cells of the innate immune system, the NLRP3 inflammasome plays an important role, as it senses and responds to a variety of exogenous and endogenous pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The NLRP3 inflammasome is responsible for the maturation and secretion of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18 and for the induction of a type of inflammatory cell death known as pyroptosis. Overactivation of the NLRP3 inflammasome can be a driver of various diseases. Since leukemia is known to be an inflammation-driven cancer and IL-1β is produced in elevated levels by leukemic cells, research on NLRP3 in the context of leukemia has increased in recent years. In this review, we summarize the current knowledge on leukemia-promoting inflammation and, in particular, the role of the NLRP3 inflammasome in different types of leukemia. Furthermore, we examine a connection between NLRP3, autophagy and leukemia.

scholarly journals The role of Toll-like receptors (TLRs) in virus-related cancers: a mini review

2020 ◽  
Vol 33 (4) ◽  
pp. 225-227
Author(s):  
Anna Dworzanska ◽  
Małgorzata Polz-Dacewicz
Keyword(s):  
Innate Immune System ◽  
Viral Infections ◽  
Research Work ◽  
Current Data ◽  
Innate Immune ◽  
Toll Like Receptors ◽  
Epstein Barr ◽  
Inflammatory Autoimmune Disease ◽  
Review Current

Abstract The modulation of the host innate immune system is a well-established carcinogenesis feature of several tumors, including human Epstein-Barr (EBV) and Papillomavirus-(HPV) related cancers. These viruses are able to interrupt the initial events of the immune response, including the expression of Toll-like receptors (TLRs), cytokines, and inflammation. The aim of the study is to review current data and summarize knowledge on the TLRs and their role in the development of cancer, especially viral-related cancers (EBV and HPV). Research work shows a correlation between the TLRs polymorphism and the development of oropharyngeal and gastric cancer (GC), especially related to viral infections. Many studies suggest the important role for TLRs in inflammatory, autoimmune disease and human cancers. However, further efforts are necessary to draw a precise conclusion.

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