scholarly journals Inflammasome and Cognitive Symptoms in Human Diseases: Biological Evidence from Experimental Research

2020 ◽  
Vol 21 (3) ◽  
pp. 1103 ◽  
Author(s):  
So Yeong Cheon ◽  
Jeongmin Kim ◽  
So Yeon Kim ◽  
Eun Jung Kim ◽  
Bon-Nyeo Koo
Keyword(s):  
Drug Target ◽  
Critical Role ◽  
The Elderly ◽  
Innate Immune ◽  
Human Diseases ◽  
Cognitive Symptoms ◽  
Inflammasome Component ◽  
Host Defense System ◽  
Infectious Pathogen ◽  
Molecular Patterns

Cognitive symptoms are prevalent in the elderly and are associated with an elevated risk of developing dementia. Disease-driven changes can cause cognitive disabilities in memory, attention, and language. The inflammasome is an innate immune intracellular complex that has a critical role in the host defense system, in that it senses infectious pathogen-associated and endogenous danger-associated molecular patterns. An unbalanced or dysregulated inflammasome is associated with infectious, inflammatory, and neurodegenerative diseases. Due to its importance in such pathological conditions, the inflammasome is an emerging drug target for human diseases. A growing number of studies have revealed links between cognitive symptoms and the inflammasome. Several studies have shown that reducing the inflammasome component mitigates cognitive symptoms in diseased states. Therefore, understanding the inflammasome regulatory mechanisms may be required for the prevention and treatment of cognitive symptoms. The purpose of this review is to discuss the current understanding of the inflammasome and its relationships with cognitive symptoms in various human diseases.

scholarly journals Inflammation and Immune Response in COPD: Where Do We Stand?

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Nikoletta Rovina ◽  
Antonia Koutsoukou ◽  
Nikolaos G. Koulouris
Keyword(s):  
Immune Responses ◽  
Bacterial Infections ◽  
Severe Disease ◽  
Critical Role ◽  
Specific Pattern ◽  
Innate Immune ◽  
Danger Signal ◽  
Cd4 Cells ◽  
Adaptive Immune ◽  
Molecular Patterns

Increasing evidence indicates that chronic inflammatory and immune responses play key roles in the development and progression of COPD. Recent data provide evidence for a role in the NLRP3 inflammasome in the airway inflammation observed in COPD. Cigarette smoke activates innate immune cells by triggering pattern recognition receptors (PRRs) to release “danger signal”. These signals act as ligands to Toll-like receptors (TLRs), triggering the production of cytokines and inducing innate inflammation. In smokers who develop COPD there appears to be a specific pattern of inflammation in the airways and parenchyma as a result of both innate and adaptive immune responses, with the predominance of CD8+ and CD4+ cells, and in the more severe disease, with the presence of lymphoid follicles containing B lymphocytes and T cells. Furthermore, viral and bacterial infections interfere with the chronic inflammation seen in stable COPD and exacerbations via pathogen-associated molecular patterns (PAMPs). Finally, autoimmunity is another novel aspect that may play a critical role in the pathogenesis of COPD. This review is un update of the currently discussed roles of inflammatory and immune responses in the pathogenesis of COPD.

Innate immune receptors in type 1 diabetes: the relationship to cell death-associated inflammation

2020 ◽  
Vol 48 (3) ◽  
pp. 1213-1225 ◽  
Author(s):  
Tae Kang Kim ◽  
Myung-Shik Lee
Keyword(s):  
Innate Immunity ◽  
Type 1 Diabetes ◽  
Inflammatory Responses ◽  
Critical Role ◽  
Innate Immune ◽  
Therapeutic Modalities ◽  
Immune Receptors ◽  
Molecular Patterns

The importance of innate immunity in host defense and inflammatory responses has been clearly demonstrated after the discovery of innate immune receptors such as Toll-like receptors (TLRs) or Nucleotide-binding oligomerization domain-containing protein (Nod)-like receptors (NLRs). Innate immunity also plays a critical role in diverse pathological conditions including autoimmune diseases such as type 1 diabetes (T1D). In particular, the role of a variety of innate immune receptors in T1D has been demonstrated using mice with targeted disruption of such innate immune receptors. Here, we discuss recent findings showing the role of innate immunity in T1D that were obtained mostly from studies of genetic mouse models of innate immune receptors. In addition, the role of innate immune receptors involved in the pathogenesis of T1D in sensing death-associated molecular patterns (DAMPs) released from dead cells or pathogen-associated molecular patterns (PAMPs) will also be covered. Elucidation of the role of innate immune receptors in T1D and the nature of DAMPs sensed by such receptors may lead to the development of new therapeutic modalities against T1D.

scholarly journals The Emerging Role of Complement Lectin Pathway in Trypanosomatids: Molecular Bases in Activation, Genetic Deficiencies, Susceptibility to Infection, and Complement System-Based Therapeutics

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Ingrid Evans-Osses ◽  
Iara de Messias-Reason ◽  
Marcel I. Ramirez
Keyword(s):  
Host Defense ◽  
Complement System ◽  
Innate Immune ◽  
Lectin Pathway ◽  
Complement Factors ◽  
Susceptibility To Infection ◽  
Host Defense System ◽  
Molecular Patterns ◽  
Molecular Components ◽  
Mannan Binding Lectin

The innate immune system is evolutionary and ancient and is the pivotal line of the host defense system to protect against invading pathogens and abnormal self-derived components. Cellular and molecular components are involved in recognition and effector mechanisms for a successful innate immune response. The complement lectin pathway (CLP) was discovered in 1990. These new components at the complement world are very efficient. Mannan-binding lectin (MBL) and ficolin not only recognize many molecular patterns of pathogens rapidly to activate complement but also display several strategies to evade innate immunity. Many studies have shown a relation between the deficit of complement factors and susceptibility to infection. The recently discovered CLP was shown to be important in host defense against protozoan microbes. Although the recognition of pathogen-associated molecular patterns by MBL and Ficolins reveal efficient complement activations, an increase in deficiency of complement factors and diversity of parasite strategies of immune evasion demonstrate the unsuccessful effort to control the infection. In the present paper, we will discuss basic aspects of complement activation, the structure of the lectin pathway components, genetic deficiency of complement factors, and new therapeutic opportunities to target the complement system to control infection.

scholarly journals The Role of Innate Immunity Receptors in the Pathogenesis of Inflammatory Bowel Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Paula Peruzzi Elia ◽  
Yolanda Faia M. Tolentino ◽  
Claudio Bernardazzi ◽  
Heitor Siffert Pereira de Souza
Keyword(s):  
Inflammatory Bowel Disease ◽  
Innate Immunity ◽  
Bowel Disease ◽  
Critical Role ◽  
Innate Immune ◽  
Gastrointestinal Mucosa ◽  
Persistent Inflammation ◽  
Nucleotide Oligomerization ◽  
Inflammatory Bowel ◽  
Molecular Patterns

Innate immunity constitutes the first line of defense, fundamental for the recognition and the initiation of an inflammatory response against microorganisms. The innate immune response relies on the sensing of microbial-associated molecular patterns through specialized structures such as toll-like receptors (TLRs) and the nucleotide oligomerization domain- (NOD-) like receptors (NLRs). In the gut, these tasks are performed by the epithelial barrier and the presence of adaptive and innate immune mechanisms. TLRs and NLRs are distributed throughout the gastrointestinal mucosa, being more expressed in the epithelium, and in lamina propria immune and nonimmune cells. These innate immunity receptors exhibit complementary biological functions, with evidence for pathways overlapping. However, as tolerance is the predominant physiological response in the gastrointestinal mucosa, it appears that the TLRs are relatively downregulated, while NLRs play a critical role in mucosal defense in the gut. Over the past two decades, genetic polymorphisms have been associated with several diseases including inflammatory bowel disease. Special emphasis has been given to the susceptibility to Crohn’s disease, in association with abnormalities in the NOD2 and in the NLRP3/inflammasome. Nevertheless, the mechanisms underlying innate immune receptors dysfunction that result in the persistent inflammation in inflammatory bowel disease remain to be clarified.

scholarly journals Structure, Function, and Regulation of the Essential Virulence Factor Capsular Polysaccharide of Vibrio vulnificus

2020 ◽  
Vol 21 (9) ◽  
pp. 3259 ◽  
Author(s):  
Gregg S. Pettis ◽  
Aheli S. Mukerji
Keyword(s):  
Coastal Waters ◽  
Capsular Polysaccharide ◽  
Vibrio Vulnificus ◽  
Critical Role ◽  
Phase Variation ◽  
Innate Immune ◽  
Repeat Sequences ◽  
Life Threatening ◽  
Inflammatory Cytokine Response ◽  
Group 1

Vibrio vulnificus populates coastal waters around the world, where it exists freely or becomes concentrated in filter feeding mollusks. It also causes rapid and life-threatening sepsis and wound infections in humans. Of its many virulence factors, it is the V. vulnificus capsule, composed of capsular polysaccharide (CPS), that plays a critical role in evasion of the host innate immune system by conferring antiphagocytic ability and resistance to complement-mediated killing. CPS may also provoke a portion of the host inflammatory cytokine response to this bacterium. CPS production is biochemically and genetically diverse among strains of V. vulnificus, and the carbohydrate diversity of CPS is likely affected by horizontal gene transfer events that result in new combinations of biosynthetic genes. Phase variation between virulent encapsulated opaque colonial variants and attenuated translucent colonial variants, which have little or no CPS, is a common phenotype among strains of this species. One mechanism for generating acapsular variants likely involves homologous recombination between repeat sequences flanking the wzb phosphatase gene within the Group 1 CPS biosynthetic and transport operon. A considerable number of environmental, genetic, and regulatory factors have now been identified that affect CPS gene expression and CPS production in this pathogen.

scholarly journals Small Molecule Inhibitors of Influenza Virus Entry

2021 ◽  
Vol 14 (6) ◽  
pp. 587
Author(s):  
Zhaoyu Chen ◽  
Qinghua Cui ◽  
Michael Caffrey ◽  
Lijun Rong ◽  
Ruikun Du
Keyword(s):  
Influenza Virus ◽  
Membrane Fusion ◽  
Small Molecule ◽  
Drug Target ◽  
Small Molecule Inhibitors ◽  
Virus Entry ◽  
Critical Role ◽  
Structural Basis ◽  
Future Directions ◽  
The Past

Hemagglutinin (HA) plays a critical role during influenza virus receptor binding and subsequent membrane fusion process, thus HA has become a promising drug target. For the past several decades, we and other researchers have discovered a series of HA inhibitors mainly targeting its fusion machinery. In this review, we summarize the advances in HA-targeted development of small molecule inhibitors. Moreover, we discuss the structural basis and mode of action of these inhibitors, and speculate upon future directions toward more potent inhibitors of membrane fusion and potential anti-influenza drugs.

scholarly journals NOD-Like Receptors: Guards of Cellular Homeostasis Perturbation during Infection

2021 ◽  
Vol 22 (13) ◽  
pp. 6714
Author(s):  
Gang Pei ◽  
Anca Dorhoi
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Current Knowledge ◽  
Protein Translation ◽  
Innate Immune ◽  
Cellular Homeostasis ◽  
Translation Block ◽  
Cytoskeleton Disruption ◽  
Molecular Patterns ◽  
Fine Tune

The innate immune system relies on families of pattern recognition receptors (PRRs) that detect distinct conserved molecular motifs from microbes to initiate antimicrobial responses. Activation of PRRs triggers a series of signaling cascades, leading to the release of pro-inflammatory cytokines, chemokines and antimicrobials, thereby contributing to the early host defense against microbes and regulating adaptive immunity. Additionally, PRRs can detect perturbation of cellular homeostasis caused by pathogens and fine-tune the immune responses. Among PRRs, nucleotide binding oligomerization domain (NOD)-like receptors (NLRs) have attracted particular interest in the context of cellular stress-induced inflammation during infection. Recently, mechanistic insights into the monitoring of cellular homeostasis perturbation by NLRs have been provided. We summarize the current knowledge about the disruption of cellular homeostasis by pathogens and focus on NLRs as innate immune sensors for its detection. We highlight the mechanisms employed by various pathogens to elicit cytoskeleton disruption, organelle stress as well as protein translation block, point out exemplary NLRs that guard cellular homeostasis during infection and introduce the concept of stress-associated molecular patterns (SAMPs). We postulate that integration of information about microbial patterns, danger signals, and SAMPs enables the innate immune system with adequate plasticity and precision in elaborating responses to microbes of variable virulence.

scholarly journals Loss of Nckx3 Exacerbates Experimental DSS-Induced Colitis in Mice through p53/NF-κB Pathway

2021 ◽  
Vol 22 (5) ◽  
pp. 2645
Author(s):  
Dinh Nam Tran ◽  
Seon Myeong Go ◽  
Seon-Mi Park ◽  
Eui-Man Jung ◽  
Eui-Bae Jeung
Keyword(s):  
Immune Response ◽  
Cellular Proliferation ◽  
Intestinal Inflammation ◽  
Critical Role ◽  
Experimental Colitis ◽  
Innate Immune ◽  
Inflammatory Conditions ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Microarray Analyses

Inflammatory bowel diseases (IBDs) comprises a range of chronic inflammatory conditions of the intestinal tract. The incidence and prevalence of IBDs are increasing worldwide, but the precise etiology of these diseases is not completely understood. Calcium signaling plays a regulatory role in cellular proliferation. Nckx3, a potassium-dependent Na+/Ca2+ exchanger, is not only expressed in the brain but also in the aortic, uterine, and intestinal tissues, which contain abundant smooth muscle cells. This study investigated the role of Nckx3 in intestinal inflammation. Microarray analyses revealed the upregulation of the innate immune response-associated genes in the duodenum of Nckx3 knockout (KO) mice. The Nckx3 KO mice also showed an increase in IBD- and tumorigenesis-related genes. Using dextran sodium sulfate (DSS)-induced experimental colitis mice models, the Nckx3 KO mice showed severe colitis. Furthermore, the pathways involving p53 and NF-κB signaling were significantly upregulated by the absence of Nckx3. Overall, Nckx3 plays a critical role in the innate immune and immune response and may be central to the pathogenesis of IBD.

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