NOD-Like Receptors: Versatile Cytosolic Sentinels

2015 ◽  
Vol 95 (1) ◽  
pp. 149-178 ◽  
Author(s):  
Vinicius Motta ◽  
Fraser Soares ◽  
Tian Sun ◽  
Dana J. Philpott
Keyword(s):  
Pattern Recognition ◽  
Molecular Mechanisms ◽  
Sea Urchins ◽  
Adaptive Immune Response ◽  
Recognition System ◽  
Biological Processes ◽  
Ligand Specificity ◽  
Adaptive Immune ◽  
Leucine Rich Repeats ◽  
Terminal Effector

Nucleotide binding oligomerization domain (NOD)-like receptors are cytoplasmic pattern-recognition receptors that together with RIG-I-like receptor (retinoic acid-inducible gene 1), Toll-like receptor (TLR), and C-type lectin families make up the innate pathogen pattern recognition system. There are 22 members of NLRs in humans, 34 in mice, and even a larger number in some invertebrates like sea urchins, which contain more than 200 receptors. Although initially described to respond to intracellular pathogens, NLRs have been shown to play important roles in distinct biological processes ranging from regulation of antigen presentation, sensing metabolic changes in the cell, modulation of inflammation, embryo development, cell death, and differentiation of the adaptive immune response. The diversity among NLR receptors is derived from ligand specificity conferred by the leucine-rich repeats and an NH2-terminal effector domain that triggers the activation of different biological pathways. Here, we describe NLR genes associated with different biological processes and the molecular mechanisms underlying their function. Furthermore, we discuss mutations in NLR genes that have been associated with human diseases.

scholarly journals Pattern Recognition Proteins: First Line of Defense Against Coronaviruses

2021 ◽  
Vol 12 ◽  
Author(s):  
Carlos A. Labarrere ◽  
Ghassan S. Kassab
Keyword(s):  
Immune Response ◽  
Pattern Recognition ◽  
Global Economy ◽  
Rna Viruses ◽  
Severe Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Recognition Protein ◽  
Pattern Recognition Protein

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host’s immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host’s innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of the pattern recognition protein (PRP) trident composed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.

Adaptive immunity

2010 ◽  
pp. 224-234
Author(s):  
Paul Klenerman
Keyword(s):  
Infectious Disease ◽  
Immune Response ◽  
Pattern Recognition ◽  
Adaptive Immunity ◽  
Adaptive Response ◽  
Critical Role ◽  
Adaptive Immune Response ◽  
Structural Features ◽  
Adaptive Immune ◽  
Single Organism

Following the innate immune response, which acts very rapidly, the adaptive immune response plays a critical role in host defence against infectious disease. Unlike the innate response, which is triggered by pattern recognition of pathogens, i.e. features that are common to many bacteria or viruses, the adaptive response is triggered by structural features—known as antigens or epitopes—that are typically unique to a single organism....

scholarly journals Proteomic and metabolomic signatures associated with the immune response in healthy individuals immunized with an inactivated SARS-CoV-2 vaccine

2021 ◽  
Author(s):  
Yi Wang ◽  
Xiaoxia Wang ◽  
Laurence Don Wai Luu ◽  
Shaojin Chen ◽  
Jin Fu ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Systems Biology ◽  
Complement Activation ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Adaptive Immune Response ◽  
Humoral Response ◽  
Tca Cycle ◽  
Adaptive Immune

CoronaVac (Sinovac), an inactivated vaccine for SARS-CoV-2, has been widely used for immunization. However, analysis of the underlying molecular mechanisms driving CoronaVac-induced immunity is still limited. Here, we applied a systems biology approach to understand the mechanisms behind the adaptive immune response to CoronaVac in a cohort of 50 volunteers immunized with 2 doses of CoronaVac. Vaccination with CoronaVac led to an integrated immune response that included several effector arms of the adaptive immune system including specific IgM/IgG, humoral response and other immune response, as well as the innate immune system as shown by complement activation. Metabolites associated with immunity were also identified implicating the role of metabolites in the humoral response, complement activation and other immune response. Networks associated with the TCA cycle and amino acids metabolic pathways, such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glycine, serine and threonine metabolism were tightly coupled with immunity. Critically, we constructed a multifactorial response network (MRN) to analyze the underlying interactions and compared the signatures affected by CoronaVac immunization and SARS-CoV-2 infection to further identify immune signatures and related metabolic pathways altered by CoronaVac immunization. These results suggest that protective immunity against SARS-CoV-2 can be achieved via multiple mechanisms and highlights the utility of a systems biology approach in defining molecular correlates of protection to vaccination.

scholarly journals Filamentation initiated by Cas2 and its association with the acquisition process in cells

2019 ◽  
Vol 11 (3) ◽  
Author(s):  
Lei Wang ◽  
Xin Yu ◽  
Mengjie Li ◽  
Guiqin Sun ◽  
Lin Zou ◽  
...  
Keyword(s):  
Oral Health ◽  
Molecular Mechanisms ◽  
Asymmetric Cell Division ◽  
Morphological Changes ◽  
Protein A ◽  
Adaptive Immune Response ◽  
Imaging Analysis ◽  
E Coli ◽  
Adaptive Immune ◽  
Oral Microflora

Abstract Cas1-and-Cas2-mediated new spacer acquisition is an essential process for bacterial adaptive immunity. The process is critical for the ecology of the oral microflora and oral health. Although molecular mechanisms for spacer acquisition are known, it has never been established if this process is associated with the morphological changes of bacteria. In this study, we demonstrated a novel Cas2-induced filamentation phenotype in E. coli that was regulated by co-expression of the Cas1 protein. A 30 amino acid motif at the carboxyl terminus of Cas2 is necessary for this function. By imaging analysis, we provided evidence to argue that Cas-induced filamentation is a step coupled with new spacer acquisition during which filaments are characterised by polyploidy with asymmetric cell division. This work may open new opportunities to investigate the adaptive immune response and microbial balance for oral health.

scholarly journals Bioorthogonal Protein Labelling Enables The Study Of Antigen Processing of Citrullinated and Carbamylated Auto-Antigens

2021 ◽  
Author(s):  
Tyrza van Leeuwen ◽  
Can Araman ◽  
Linda Pieper Pournara ◽  
Arieke S.B. Kampstra ◽  
Thomas Bakkum ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Antigen Processing ◽  
Adaptive Immune Response ◽  
Short Peptides ◽  
Biological Processes ◽  
Protein Labelling ◽  
Adaptive Immune ◽  
Antigenic Material

Proteolysis is fundamental to many biological processes. In the immune system, it underpins the activation of the adaptive immune response: degradation of antigenic material into short peptides and presentation thereof...

scholarly journals Understanding neutropenia secondary to intrinsic or iatrogenic immune dysregulation

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 504-513
Author(s):  
Kelly Walkovich ◽  
James A. Connelly
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Immune Checkpoint Inhibitors ◽  
Molecular Mechanisms ◽  
Checkpoint Inhibitors ◽  
Adaptive Immune Response ◽  
Immune Dysregulation ◽  
Inborn Errors ◽  
T Cell Therapy ◽  
Adaptive Immune

Abstract As a key member of the innate and adaptive immune response, neutrophils provide insights into the hematopoietic and inflammatory manifestations of inborn errors of immunity (IEI) and the consequences of immunotherapy. The facile recognition of IEI presenting with neutropenia provides an avenue for hematologists to facilitate early diagnosis and expedite biologically rationale care. Moreover, enhancing the understanding of the molecular mechanisms driving neutropenia in IEI—decreased bone marrow reserves, diminished egress from the bone marrow, and decreased survival—offers an opportunity to further dissect the pathophysiology driving neutropenia secondary to iatrogenic immune dysregulation, eg, immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy.

scholarly journals Netrin-1: A Modulator of Acute and Chronic Inflammation

2021 ◽  
Vol 23 (1) ◽  
pp. 275
Author(s):  
Laura Ziegon ◽  
Martin Schlegel
Keyword(s):  
Chronic Inflammation ◽  
Neuronal Development ◽  
Adaptive Immune Response ◽  
Immune Defense ◽  
Acute Injury ◽  
Biological Processes ◽  
First Line ◽  
Adaptive Immune ◽  
The Family ◽  
Acute And Chronic Inflammation

Netrins belong to the family of laminin-like secreted proteins, which guide axonal migration and neuronal growth in the developing central nervous system. Over the last 20 years, it has been established that netrin-1 acts as a chemoattractive or chemorepulsive cue in diverse biological processes far beyond neuronal development. Netrin-1 has been shown to play a central role in cell adhesion, cell migration, proliferation, and cell survival in neuronal and non-neuronal tissue. In this context, netrin-1 was found to orchestrate organogenesis, angiogenesis, tumorigenesis, and inflammation. In inflammation, as in neuronal development, netrin-1 plays a dichotomous role directing the migration of leukocytes, especially monocytes in the inflamed tissue. Monocyte-derived macrophages have long been known for a similar dual role in inflammation. In response to pathogen-induced acute injury, monocytes are rapidly recruited to damaged tissue as the first line of immune defense to phagocyte pathogens, present antigens to initiate the adaptive immune response, and promote wound healing in the resolution phase. On the other hand, dysregulated macrophages with impaired phagocytosis and egress capacity accumulate in chronic inflammation sites and foster the maintenance—and even the progression—of chronic inflammation. In this review article, we will highlight the dichotomous roles of netrin-1 and its impact on acute and chronic inflammation.

scholarly journals Bioorthogonal antigens allow the unbiased study of antigen processing and presentation

2018 ◽  
Author(s):  
Can Araman ◽  
Linda Pieper-Pournara ◽  
Tyrza van Leeuwen ◽  
Arieke S. B. Kampstra ◽  
Thomas Bakkum ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Antigen Processing ◽  
Adaptive Immune Response ◽  
Short Peptides ◽  
Biological Processes ◽  
Adaptive Immune ◽  
Major Histocompatibility Complexes ◽  
Antigenic Material ◽  
Antigen Processing And Presentation

AbstractProteolysis is fundamental to many biological processes. In the immune system, it underpins the activation of the adaptive immune response: degradation of antigenic material into short peptides and presentation thereof on major histocompatibility complexes, leads to activation of T-cells. This initiates the adaptive immune response against many pathogens.

scholarly journals Immunological Roles of NLR in Allergic Diseases and Its Underlying Mechanisms

2021 ◽  
Vol 22 (4) ◽  
pp. 1507
Author(s):  
Miranda Sin-Man Tsang ◽  
Tianheng Hou ◽  
Ben Chung-Lap Chan ◽  
Chun Kwok Wong
Keyword(s):  
Molecular Mechanisms ◽  
Immune Surveillance ◽  
Adaptive Immune Response ◽  
Allergic Inflammation ◽  
Allergic Diseases ◽  
Adaptive Immune ◽  
The Past ◽  
Underlying Mechanisms ◽  
Oligomerization Domain

Our understanding on the immunological roles of pathogen recognition in innate immunity has vastly increased over the past 20 years. Nucleotide-binding oligomerization domain (NOD)-like receptors (NLR) are cytosolic pattern recognition receptors (PRR) that are responsible for sensing microbial motifs and endogenous damage signals in mammalian cytosol for immune surveillance and host defense. The accumulating discoveries on these NLR sensors in allergic diseases suggest that the pathogenesis of allergic diseases may not be confined to the adaptive immune response. Therapy targeting NLR in murine models also shields light on its potential in the treatment of allergies in man. In this review, we herein summarize the recent understanding of the role of NLR sensors and their molecular mechanisms involved in allergic inflammation, including atopic dermatitis and allergic asthma.

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