Review: Soluble innate immune pattern-recognition proteins for clearing dying cells and cellular components: implications on exacerbating or resolving inflammation

2010 ◽  
Vol 16 (3) ◽  
pp. 191-200 ◽  
Author(s):  
Michael L. Litvack ◽  
Nades Palaniyar
Keyword(s):  
Pattern Recognition ◽  
Cell Death ◽  
Treatment Strategies ◽  
Innate Immune ◽  
Live Cells ◽  
Death Process ◽  
Clear Understanding ◽  
Phagocytic Cells ◽  
Molecular Patterns ◽  
Dying Cells

Soluble innate immune pattern-recognition proteins (sPRPs) identify non-self or altered-self molecular patterns. Dying cells often display altered-self arrays of molecules on their surfaces. Hence, sPRPs are ideal for recognizing these cells and their components. Dying cell surfaces often contain, or allow the access to different lipids, intracellular glycoproteins and nucleic acids such as DNA at different stages of cell death. These are considered as ‘eat me’ signals that replace the native ‘don’t eat me’ signals such as CD31, CD47 present on the live cells. A programmed cell death process such as apoptosis also generates cell surface blebs that contain intracellular components. These blebs are easily released for effective clearance or signalling. During late stages of cell death, soluble components are also released that act as ‘find me’ signal (e.g. LysoPC, nucleotides). The sPRPs such as collectins, ficolins, pentraxins, sCD14, MFG-E8, natural IgM and C1q can effectively identify some of these specific molecular patterns. The biological end-point is different depending on sPRP, tissue, stage of apoptosis and the type of cell death. The sPRPs that reside in the immune-privileged surfaces such as lungs often act as opsonins and enhance a silent clearance of dying cells and cellular material by macrophages and other phagocytic cells. Although the recognition of these materials by complement-activating proteins could amplify the opsonic signal, this pathway may aggravate inflammation. Clear understanding of the involvement of specific sPRPs in cell death and subsequent clearance of dying cell and their components is essential for devising appropriate treatment strategies for diseases involving infection, inflammation and auto-antibody generation.

Internucleosomal DNA fragmentation and programmed cell death (apoptosis) in the interdigital tissue of the embryonic chick leg bud

1993 ◽  
Vol 106 (1) ◽  
pp. 201-208 ◽  
Author(s):  
V. Garcia-Martinez ◽  
D. Macias ◽  
Y. Ganan ◽  
J.M. Garcia-Lobo ◽  
M.V. Francia ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Dna Fragmentation ◽  
Limb Development ◽  
Light Transmission ◽  
Morphological Changes ◽  
Death Process ◽  
Chondrogenic Potential ◽  
Cell Death Process ◽  
Dying Cells

In this work we have attempted to characterize the programmed cell death process in the chick embryonic interdigital tissue. Interdigital cell death is a prominent phenomenon during limb development and has the role of sculpturing the digits. Morphological changes in the regressing interdigital tissue studied by light, transmission and scanning electron microscopy were correlated with the occurrence of internucleosomal DNA fragmentation, evaluated using agarose gels. Programming of the cell death process was also analyzed by testing the chondrogenic potential of the interdigital mesenchyme, in high density cultures. Our results reveal a progressive loss of the chondrogenic potential of the interdigital mesenchyme, detectable 36 hours before the onset of the degenerative process. Internucleosomal DNA fragmentation was only detected concomitant with the appearance of cells dying with the morphology of apoptosis, but unspecific DNA fragmentation was also present at the same time. This unspecific DNA fragmentation was explained by a precocious activation of the phagocytic removal of the dying cells, confirmed in the tissue sections. From our observations it is suggested that programming of cell death involves changes before endonuclease activation. Further, cell surface changes involved in the phagocytic uptake of the dying cells appear to be as precocious as endonuclease activation.

scholarly journals Therapeutic Interventions into Innate Immune Diseases by Means of Aptamers

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 955
Author(s):  
Farzana Yasmeen ◽  
Hana Seo ◽  
Nasir Javaid ◽  
Moon Suk Kim ◽  
Sangdun Choi
Keyword(s):  
Pattern Recognition ◽  
Immune System ◽  
Crucial Role ◽  
Innate Immune System ◽  
Innate Immune ◽  
Therapeutic Interventions ◽  
Immune System Diseases ◽  
Target Molecules ◽  
Molecular Patterns ◽  
Recognition Receptor

The immune system plays a crucial role in the body’s defense system against various pathogens, such as bacteria, viruses, and parasites, as well as recognizes non-self- and self-molecules. The innate immune system is composed of special receptors known as pattern recognition receptors, which play a crucial role in the identification of pathogen-associated molecular patterns from diverse microorganisms. Any disequilibrium in the activation of a particular pattern recognition receptor leads to various inflammatory, autoimmune, or immunodeficiency diseases. Aptamers are short single-stranded deoxyribonucleic acid or ribonucleic acid molecules, also termed “chemical antibodies,” which have tremendous specificity and affinity for their target molecules. Their features, such as stability, low immunogenicity, ease of manufacturing, and facile screening against a target, make them preferable as therapeutics. Immune-system–targeting aptamers have a great potential as a targeted therapeutic strategy against immune diseases. This review summarizes components of the innate immune system, aptamer production, pharmacokinetic characteristics of aptamers, and aptamers related to innate-immune-system diseases.

scholarly journals Phytophthora infestans RXLR-WY effector AVR3a associates with a Dynamin-Related Protein involved in endocytosis of a plant pattern recognition receptor

2014 ◽  
Author(s):  
Angela Chaparro-Garcia ◽  
Simon Schwizer ◽  
Jan Sklenar ◽  
Kentaro Yoshida ◽  
Jorunn I. B. Bos ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Cell Death ◽  
Phytophthora Infestans ◽  
Plant Pathogens ◽  
Defense Responses ◽  
Effector Proteins ◽  
Related Protein ◽  
Receptor Mediated Endocytosis ◽  
Molecular Patterns ◽  
Basal Immunity

Perception of pathogen associated molecular patterns (PAMPs) by cell surface localized pattern recognition receptors (PPRs), activates plant basal defense responses in a process known as PAMP/PRR–triggered immunity (PTI). In turn, pathogens deploy effector proteins that interfere with different steps in PTI signaling. However, our knowledge of PTI suppression by filamentous plant pathogens, i.e. fungi and oomycetes, remains fragmentary. Previous work revealed that BAK1/SERK3, a regulatory receptor of several PRRs, contributes to basal immunity against the Irish potato famine pathogen Phytophthora infestans. Moreover BAK1/SERK3 is required for the cell death induced by P. infestans elicitin INF1, a protein with characteristics of PAMPs. The P. infestans host-translocated RXLR-WY effector AVR3a is known to supress INF1-mediated defense by binding the E3 ligase CMPG1. In contrast, AVR3aKI-Y147del, a deletion mutant of the C-terminal tyrosine of AVR3a, fails to bind CMPG1 and suppress INF1 cell death. Here we studied the extent to which AVR3a and its variants perturb additional BAK1/SERK3 dependent PTI responses using the plant PRR FLAGELLIN SENSING 2 (FLS2). We found that all tested variants of AVR3a, including AVR3aKI-Y147del, suppress early defense responses triggered by the bacterial flagellin-derived peptide flg22 and reduce internalization of activated FLS2 from the plasma membrane without disturbing its nonactivated localization. Consistent with this effect of AVR3a on FLS2 endocytosis, we discovered that AVR3a associates with the Dynamin-Related Protein DRP2, a plant GTPase implicated in receptor-mediated endocytosis. Interestingly, DRP2 is required for ligand-induced FLS2 internalization but does not affect internalization of the growth receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1). Furthermore, overexpression of DRP2 suppressed accumulation of reactive oxygen species triggered by PAMP treatment. We conclude that AVR3a associates with a key cellular trafficking and membrane-remodeling complex involved in immune receptor-mediated endocytosis and signaling. AVR3a is a multifunctional effector that can suppress BAK1/SERK3 mediated immunity through at least two different pathways.

scholarly journals Nuclease activities and cell death processes associated with the development of surface cultures of Streptomyces antibioticus ETH 7451

Microbiology ◽  
2002 ◽  
Vol 148 (2) ◽  
pp. 405-412 ◽  
Author(s):  
Marisol Fernández ◽  
Jesús Sánchez
Keyword(s):  
Cell Death ◽  
Aerial Mycelium ◽  
Dna Degradation ◽  
Death Process ◽  
Chromosomal Dna ◽  
Developmentally Regulated ◽  
Streptomyces Antibioticus ◽  
Viability Assay ◽  
Green Fluorescent ◽  
Dying Cells

The presence and significance of developmentally regulated nucleases in Streptomyces antibioticus ETH 7451 has been studied in relation to the lytic processes occurring during differentiation. The cell-death processes have been followed in surface cultures by a propidium iodide viability assay. This has allowed the visualization of dead (membrane-damaged, red fluorescent) and live (membrane-intact, green fluorescent) mycelium during development, and has facilitated the analysis of the role of nucleases in these processes. A parallel activity-gel analysis showed the appearance of 20–22 kDa, 34 kDa and 44 kDa nucleases, the latter appearing only when aerial mycelium is formed. The appearance of these nucleases shows a remarkable correlation with the death process of the mycelium during differentiation and with chromosomal DNA degradation. The 20–22 kDa enzymes are possibly related to the lytic phenomena taking place in the vegetative substrate mycelium before the emergence of the reproductive aerial mycelium, whereas the function of the 44 kDa nuclease seems to be related to the sporulation step. The 20–22 kDa nucleases require Ca2+ for activity and are inhibited by Zn2+. The nucleases are loosely bound to the cell wall from where they can be liberated by simple washing. Conceivably, these enzymes work together and co-ordinate to achieve an efficient hydrolysis of DNA from dying cells. The results show that the biochemical reactions related with the lytic DNA degradation during the programmed cell death are notably conserved in Streptomyces. Some of the features of the process and the biochemical characteristics of the enzymes involved are analogous to those taking place during the DNA fragmentation processes in eukaryotic apoptotic cells.

scholarly journals Defective efferocytosis as a predictor of COVID-19 mortality

2021 ◽  
Author(s):  
Adnan Erol
Keyword(s):  
Apoptotic Cell ◽  
Treatment Options ◽  
Innate Immune ◽  
Phagocytic Cells ◽  
Secondary Necrosis ◽  
Organ Failures ◽  
Infected Cells ◽  
Severity Of The Disease ◽  
Dying Cells ◽  
Treatment Alternatives

COVID-19 is a generally benign coronavirus disease that can spread rapidly, except for those with a group of risk factors. Since the pathogenesis responsible for the severity of the disease has not been clearly revealed, effective treatment alternatives has not been developed. The hallmark of the SARS-CoV-2-infected cells is apoptosis. Apoptotic cells are cleared through a sterile process defined as efferocytosis by professional and nonprofessional phagocytic cells. The disease would be rapidly brought under control in the organism that can achieve effective efferocytosis, which is also a kind of innate immune response. In the risk group, the efferocytic process is defective. By the addition of the apoptotic cell load associated with SARS-COV-2 infection, failure to achieve efferocytosis of dying cells can initiate secondary necrosis that is a highly destructive process. Uncontrolled inflammation and coagulation abnormalities caused by secondary necrosis reason in various organ failures, lung in particular, which are responsible for the poor prognosis. Following the short and simplified information, this opinion paper aims to present possible treatment options that can control the severity of COVID-19 by detailing the mechanisms that can cause defective efferocytosis.

scholarly journals The Role of Syk/CARD9-Coupled C-Type Lectin Receptors in Immunity toMycobacterium tuberculosisInfections

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Mohlopheni Jackson Marakalala ◽  
Lisa M. Graham ◽  
Gordon D. Brown
Keyword(s):  
Immune Response ◽  
Pattern Recognition ◽  
Mycobacterium Tuberculosis ◽  
Immune Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Lectin Receptors ◽  
Molecular Patterns

There is increasing interest in understanding the mechanisms underlying the interactions that occur betweenMycobacterium tuberculosisand host innate immune cells. These cells express pattern recognition receptors (PRRs) which recognise mycobacterial pathogen-associated molecular patterns (PAMPs) and which can influence the host immune response to the infection. Although many of the PRRs appear to be redundant in the control ofM. tuberculosisinfectionin vivo, recent discoveries have revealed a key, nonredundant, role of the Syk/CARD9 signalling pathway in antimycobacterial immunity. Here we review these discoveries, as well as recent data investigating the role of the Syk/CARD9-coupled PRRs that have been implicated in mycobacterial recognition, including Dectin-1 and Mincle.

Inhibitory pattern recognition receptors

2021 ◽  
Vol 219 (1) ◽  
Author(s):  
Matevž Rumpret ◽  
Helen J. von Richthofen ◽  
Victor Peperzak ◽  
Linde Meyaard
Keyword(s):  
Pattern Recognition ◽  
Cell Death ◽  
Immune System ◽  
Immune Responses ◽  
Pattern Recognition Receptors ◽  
Inhibitory Receptors ◽  
Danger Signals ◽  
Molecular Pattern ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns

Pathogen- and damage-associated molecular patterns are sensed by the immune system’s pattern recognition receptors (PRRs) upon contact with a microbe or damaged tissue. In situations such as contact with commensals or during physiological cell death, the immune system should not respond to these patterns. Hence, immune responses need to be context dependent, but it is not clear how context for molecular pattern recognition is provided. We discuss inhibitory receptors as potential counterparts to activating pattern recognition receptors. We propose a group of inhibitory pattern recognition receptors (iPRRs) that recognize endogenous and microbial patterns associated with danger, homeostasis, or both. We propose that recognition of molecular patterns by iPRRs provides context, helps mediate tolerance to microbes, and helps balance responses to danger signals.

scholarly journals Scavenging nucleic acid debris to combat autoimmunity and infectious disease

2016 ◽  
Vol 113 (35) ◽  
pp. 9728-9733 ◽  
Author(s):  
Eda K. Holl ◽  
Kara L. Shumansky ◽  
Luke B. Borst ◽  
Angela D. Burnette ◽  
Christopher J. Sample ◽  
...  
Keyword(s):  
Immune System ◽  
Nucleic Acid ◽  
Innate Immune ◽  
Nucleic Acid Binding ◽  
Downstream Effector ◽  
Wide Range ◽  
Molecular Patterns ◽  
Dying Cells ◽  
Damage Associated Molecular Patterns ◽  
Lethal Doses

Nucleic acid-containing debris released from dead and dying cells can be recognized as damage-associated molecular patterns (DAMPs) or pattern-associated molecular patterns (PAMPs) by the innate immune system. Inappropriate activation of the innate immune response can engender pathological inflammation and autoimmune disease. To combat such diseases, major efforts have been made to therapeutically target the pattern recognition receptors (PRRs) such as the Toll-like receptors (TLRs) that recognize such DAMPs and PAMPs, or the downstream effector molecules they engender, to limit inflammation. Unfortunately, such strategies can limit the ability of the immune system to combat infection. Previously, we demonstrated that nucleic acid-binding polymers can act as molecular scavengers and limit the ability of artificial nucleic acid ligands to activate PRRs. Herein, we demonstrate that nucleic acid scavengers (NASs) can limit pathological inflammation and nucleic acid-associated autoimmunity in lupus-prone mice. Moreover, we observe that such NASs do not limit an animal’s ability to combat viral infection, but rather their administration improves survival when animals are challenged with lethal doses of influenza. These results indicate that molecules that scavenge extracellular nucleic acid debris represent potentially safer agents to control pathological inflammation associated with a wide range of autoimmune and infectious diseases.

scholarly journals Pyroptotic and Necroptotic Cell Death in the Tumor Microenvironment and Their Potential to Stimulate Anti-Tumor Immune Responses

2021 ◽  
Vol 11 ◽  
Author(s):  
Allan Scarpitta ◽  
Ulrich T. Hacker ◽  
Hildegard Büning ◽  
Olivier Boyer ◽  
Sahil Adriouch
Keyword(s):  
Cell Death ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Immune Cells ◽  
Immunogenic Cell Death ◽  
Chemotherapeutic Drugs ◽  
Immune Functions ◽  
Molecular Patterns ◽  
Dying Cells ◽  
Damage Associated Molecular Patterns

Cancer remains the second most common cause of death worldwide affecting around 10 million patients every year. Among the therapeutic options, chemotherapeutic drugs are widely used but often associated with side effects. In addition, toxicity against immune cells may hamper anti-tumor immune responses. Some chemotherapeutic drugs, however, preserve immune functions and some can even stimulate anti-tumor immune responses through the induction of immunogenic cell death (ICD) rather than apoptosis. ICD stimulates the immune system by several mechanisms including the release of damage-associated molecular patterns (DAMPs) from dying cells. In this review, we will discuss the consequences of inducing two recently characterized forms of ICD, i.e., pyroptosis and necroptosis, in the tumor microenvironment (TME) and the perspectives they may offer to increase the immunogenicity of the so-called cold tumors and to stimulate effective anti-tumor immune responses.

scholarly journals Cell Death and Inflammation: The Role of Mitochondria in Health and Disease

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 537
Author(s):  
Anna Picca ◽  
Riccardo Calvani ◽  
Hélio José Coelho-Junior ◽  
Emanuele Marzetti
Keyword(s):  
Cell Death ◽  
Mitochondrial Dynamics ◽  
Cpg Islands ◽  
Innate Immune ◽  
Low Grade ◽  
Interferon Production ◽  
Cellular Processes ◽  
Molecular Pattern ◽  
Extracellular Compartment ◽  
Dying Cells

Mitochondria serve as a hub for a multitude of vital cellular processes. To ensure an efficient deployment of mitochondrial tasks, organelle homeostasis needs to be preserved. Mitochondrial quality control (MQC) mechanisms (i.e., mitochondrial dynamics, biogenesis, proteostasis, and autophagy) are in place to safeguard organelle integrity and functionality. Defective MQC has been reported in several conditions characterized by chronic low-grade inflammation. In this context, the displacement of mitochondrial components, including mitochondrial DNA (mtDNA), into the extracellular compartment is a possible factor eliciting an innate immune response. The presence of bacterial-like CpG islands in mtDNA makes this molecule recognized as a damaged-associated molecular pattern by the innate immune system. Following cell death-triggering stressors, mtDNA can be released from the cell and ignite inflammation via several pathways. Crosstalk between autophagy and apoptosis has emerged as a pivotal factor for the regulation of mtDNA release, cell's fate, and inflammation. The repression of mtDNA-mediated interferon production, a powerful driver of immunological cell death, is also regulated by autophagy-apoptosis crosstalk. Interferon production during mtDNA-mediated inflammation may be exploited for the elimination of dying cells and their conversion into elements driving anti-tumor immunity.

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