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Frontiers in Immunology 2020Phagocytosis is an ancient, highly conserved process in all multicellular organisms, through which the host can protect itself against invading microorganisms and... (Review)
Review
Phagocytosis is an ancient, highly conserved process in all multicellular organisms, through which the host can protect itself against invading microorganisms and environmental particles, as well as remove self-apoptotic cells/cell debris to maintain tissue homeostasis. In crustacean, phagocytosis by hemocyte has also been well-recognized as a crucial defense mechanism for the host against infectious agents such as bacteria and viruses. In this review, we summarized the current knowledge of hemocyte-mediated phagocytosis, in particular focusing on the related receptors for recognition and internalization of pathogens as well as the downstream signal pathways and intracellular regulators involved in the process of hemocyte phagocytosis. We attempted to gain a deeper understanding of the phagocytic mechanism of different hemocytes and their contribution to the host defense immunity in crustaceans.
Topics: Animals; Cell Adhesion Molecules; Crustacea; Hemocytes; Host-Pathogen Interactions; Immunity, Innate; Lectins; Opsonin Proteins; Phagocytes; Phagocytosis; Phagosomes; Pore Forming Cytotoxic Proteins; Receptors, Pattern Recognition; Receptors, Scavenger; Signal Transduction
PubMed: 32194551
DOI: 10.3389/fimmu.2020.00268 -
Frontiers in Immunology 2020Understanding the effects mediated by a set of nanoparticle (NP)-bound host biomolecules, often indicated with the term of , is essential in nanomedicine,... (Review)
Review
Understanding the effects mediated by a set of nanoparticle (NP)-bound host biomolecules, often indicated with the term of , is essential in nanomedicine, nanopharmacology, and nanotoxicology. Among the NP-adsorbed , some factors mediate cell binding, endocytosis, and clearing by macrophages and other phagocytes (opsonins), while some others display few affinities for the cell surface (dysopsonins). The functional mapping of opsonins and dysopsonins is instrumental to design long-circulating and nanotoxicologically safe next-generation nanotheranostics. In this review, we critically analyze functional data identifying specific proteins with opsonin or dysopsonin properties. Special attention is dedicated to the following: (1) the simplicity or complexity of the NP proteome and its modulation, (2) the role of specific host proteins in mediating the stealth properties of uncoated or polymer-coated NPs, and (3) the ability of the innate immune system, and, in particular, of the complement proteins, to mediate NP clearance by phagocytes. Emerging species-specific peculiarities, differentiating humans from preclinical animal models (the murine especially), are highlighted throughout this overview. The operative definition of opsonin and dysopsonin and the measurement schemes to assess their efficacy is critically re-examined. This provides a shared and unbiased approach useful for NP opsonin and dysopsonin systematic identification.
Topics: Animals; Carrier Proteins; Complement System Proteins; Guidelines as Topic; Humans; Immunomodulation; Macrophages; Nanoparticles; Opsonin Proteins; Phagocytes; Protein Binding; Proteome; Theranostic Nanomedicine
PubMed: 33154748
DOI: 10.3389/fimmu.2020.567365 -
Current Opinion in Rheumatology Sep 2014Systemic lupus erythematosus (SLE) is characterized by autoantibodies directed against nuclear autoantigens normally concealed from immune recognition in healthy... (Review)
Review
PURPOSE OF REVIEW
Systemic lupus erythematosus (SLE) is characterized by autoantibodies directed against nuclear autoantigens normally concealed from immune recognition in healthy individuals. Here, we summarize recently identified mechanisms of abnormal cell death leading to exposure and aberrant processing of nucleoprotein self antigens, and discuss their role in the SLE pathogenesis.
RECENT FINDINGS
During the past few years, the unveiling of several new forms of cell death has expanded our understanding beyond the simple view of 'apoptotic' versus 'necrotic' cell death. SLE patients show abnormalities in cell death at several levels, including increased rates of apoptosis, necrosis, and autophagy, as well as reduced clearance of dying cells. These abnormalities lead to an increased autoantigen burden and antigen modifications, such as nucleic acid oxidation that increases the inflammatory properties of self antigens. Recent investigations have highlighted the role of opsonins in determining the immunogenic versus tolerogenic characteristics of self antigens.
SUMMARY
Dysregulation of different forms of programmed cell death contributes to increased exposure, availability, and immunogenic characteristics of intracellular self antigens, which all participate in development of lupus autoimmunity. As our understanding of abnormalities of cell death in SLE advances, potential therapeutic opportunities await human implementation.
Topics: Apoptosis; Autophagy; Cell Death; Humans; Lupus Erythematosus, Systemic; MicroRNAs; Models, Biological; Necrosis; Opsonin Proteins; Receptors, Cell Surface
PubMed: 25036095
DOI: 10.1097/BOR.0000000000000083 -
Clinical and Vaccine Immunology : CVI Jun 2017Immunity to pneumococcal infections is impaired in older people, and current vaccines are poorly protective against pneumococcal disease in this population. Naturally... (Review)
Review
Immunity to pneumococcal infections is impaired in older people, and current vaccines are poorly protective against pneumococcal disease in this population. Naturally acquired immunity to pneumococcal capsular polysaccharides develops during childhood and is robust in young adults but deteriorates with advanced age. In particular, antibody levels and function are reduced in older people. Pneumococcal vaccines are recommended for people >65 years old. However, the benefits of polysaccharide and protein-conjugated vaccines in this population are small, because of both serotype replacement and incomplete protection against vaccine serotype pneumococcal disease. In this review, we overview the immune mechanisms by which naturally acquired and vaccine-induced pneumococcal capsular polysaccharide immunity declines with age, including altered colonization dynamics, reduced opsonic activity of antibodies (particularly IgM), and impaired mucosal immunity.
Topics: Age Factors; Aged; Aged, 80 and over; Antibodies, Bacterial; Bacterial Capsules; Carrier State; Humans; Immunity, Mucosal; Opsonin Proteins; Pneumococcal Infections; Streptococcus pneumoniae
PubMed: 28424198
DOI: 10.1128/CVI.00004-17 -
International Journal of Molecular... Feb 2018The traditional view of integrins portrays these highly conserved cell surface receptors as mediators of cellular attachment to the extracellular matrix (ECM), and to a... (Review)
Review
The traditional view of integrins portrays these highly conserved cell surface receptors as mediators of cellular attachment to the extracellular matrix (ECM), and to a lesser degree, as coordinators of leukocyte adhesion to the endothelium. These canonical activities are indispensable; however, there is also a wide variety of integrin functions mediated by non-ECM ligands that transcend the traditional roles of integrins. Some of these unorthodox roles involve cell-cell interactions and are engaged to support immune functions such as leukocyte transmigration, recognition of opsonization factors, and stimulation of neutrophil extracellular traps. Other cell-cell interactions mediated by integrins include hematopoietic stem cell and tumor cell homing to target tissues. Integrins also serve as cell-surface receptors for various growth factors, hormones, and small molecules. Interestingly, integrins have also been exploited by a wide variety of organisms including viruses and bacteria to support infectious activities such as cellular adhesion and/or cellular internalization. Additionally, the disruption of integrin function through the use of soluble integrin ligands is a common strategy adopted by several parasites in order to inhibit blood clotting during hematophagy, or by venomous snakes to kill prey. In this review, we strive to go beyond the matrix and summarize non-ECM ligands that interact with integrins in order to highlight these non-traditional functions of integrins.
Topics: Animals; Cell Communication; Cell Movement; Endothelium; Extracellular Matrix; Extracellular Traps; Gene Expression Regulation; Hormones; Humans; Integrins; Intercellular Signaling Peptides and Proteins; Leukocytes; Ligands; Opsonin Proteins; Protein Binding; Signal Transduction; Snake Venoms; Viral Proteins
PubMed: 29393909
DOI: 10.3390/ijms19020449 -
Frontiers in Immunology 2021Mammalian phagocytes can phagocytose (i.e. eat) other mammalian cells in the body if they display certain signals, and this phagocytosis plays fundamental roles in... (Review)
Review
Mammalian phagocytes can phagocytose (i.e. eat) other mammalian cells in the body if they display certain signals, and this phagocytosis plays fundamental roles in development, cell turnover, tissue homeostasis and disease prevention. To phagocytose the correct cells, phagocytes must discriminate which cells to eat using a 'phagocytic code' - a set of over 50 known phagocytic signals determining whether a cell is eaten or not - comprising find-me signals, eat-me signals, don't-eat-me signals and opsonins. Most opsonins require binding to eat-me signals - for example, the opsonins galectin-3, calreticulin and C1q bind asialoglycan eat-me signals on target cells - to induce phagocytosis. Some proteins act as 'self-opsonins', while others are 'negative opsonins' or 'phagocyte suppressants', inhibiting phagocytosis. We review known phagocytic signals here, both established and novel, and how they integrate to regulate phagocytosis of several mammalian targets - including excess cells in development, senescent and aged cells, infected cells, cancer cells, dead or dying cells, cell debris and neuronal synapses. Understanding the phagocytic code, and how it goes wrong, may enable novel therapies for multiple pathologies with too much or too little phagocytosis, such as: infectious disease, cancer, neurodegeneration, psychiatric disease, cardiovascular disease, ageing and auto-immune disease.
Topics: Animals; Calreticulin; Cellular Senescence; Humans; Intercellular Adhesion Molecule-3; Opsonin Proteins; Phagocytosis; Phosphatidylserines; Polysaccharides; Signal Transduction; Synapses
PubMed: 34177884
DOI: 10.3389/fimmu.2021.629979 -
Frontiers in Immunology 2023C-reactive protein (CRP) is one of the major members of the family of acute phase proteins (APP). Interest in this CRP was the result of a seminal discovery of its... (Review)
Review
C-reactive protein (CRP) is one of the major members of the family of acute phase proteins (APP). Interest in this CRP was the result of a seminal discovery of its pattern of response to pneumococcal infection in humans. CRP has the unique property of reacting with phosphocholine-containing substances, such as pneumococcal C-polysaccharide, in the presence of Ca. The attention regarding the origin of CRP and its multifunctionality has gripped researchers for several decades. The reason can be traced to the integrated evolution of CRP in the animal kingdom. CRP has been unequivocally listed as a key indicator of infectious and inflammatory diseases including autoimmune diseases. The first occurrence of CRP in the evolutionary ladder appeared in arthropods followed by molluscs and much later in the chordates. The biological significance of CRP has been established in the animal kingdom starting from invertebrates. Interestingly, the site of synthesis of CRP is mainly the liver in vertebrates, while in invertebrates it is located in diverse tissues. CRP is a multifunctional player in the scenario of innate immunity. CRP acts as an opsonin in the area of complement activation and phagocytosis. Interestingly, CRP upregulates and downregulates both cytokine production and chemotaxis. Considering various studies of CRP in humans and non-human animals, it has been logically proposed that CRP plays a common role in animals. CRP also interacts with Fcγ receptors and triggers the inflammatory response of macrophages. CRP in other animals such as primates, fish, echinoderms, arthropods, and molluscs has also been studied in some detail which establishes the evolutionary significance of CRP. In mammals, the increase in CRP levels is an induced response to inflammation or trauma; interestingly, in arthropods and molluscs, CRP is constitutively expressed and represents a major component of their hemolymph. Investigations into the primary structure of CRP from various species revealed the overall relatedness between vertebrate and invertebrate CRP. Invertebrates lack an acquired immune response; they are therefore dependent on the multifunctional role of CRP leading to the evolutionary success of the invertebrate phyla.
Topics: Animals; C-Reactive Protein; Inflammation; Invertebrates; Mammals; Opsonin Proteins; Phagocytosis; Humans
PubMed: 37860004
DOI: 10.3389/fimmu.2023.1238411 -
Frontiers in Immunology 2022The complement system is part of the innate immune system. The crucial step in activating the complement system is the generation and regulation of C3 convertase... (Review)
Review
The complement system is part of the innate immune system. The crucial step in activating the complement system is the generation and regulation of C3 convertase complexes, which are needed to generate opsonins that promote phagocytosis, to generate C3a that regulates inflammation, and to initiate the lytic terminal pathway through the generation and activity of C5 convertases. A growing body of evidence has highlighted the interplay between the complement system, coagulation system, platelets, neutrophils, and endothelial cells. The kidneys are highly susceptible to complement-mediated injury in several genetic, infectious, and autoimmune diseases. Atypical hemolytic uremic syndrome (aHUS) and lupus nephritis (LN) are both characterized by thrombosis in the glomerular capillaries of the kidneys. In aHUS, congenital or acquired defects in complement regulators may trigger platelet aggregation and activation, resulting in the formation of platelet-rich thrombi in the kidneys. Because glomerular vasculopathy is usually noted with immunoglobulin and complement accumulation in LN, complement-mediated activation of tissue factors could partly explain the autoimmune mechanism of thrombosis. Thus, kidney glomerular capillary thrombosis is mediated by complement dysregulation and may also be associated with complement overactivation. Further investigation is required to clarify the interaction between these vascular components and develop specific therapeutic approaches.
Topics: Atypical Hemolytic Uremic Syndrome; Capillaries; Complement C3-C5 Convertases; Complement System Proteins; Endothelial Cells; Humans; Kidney; Opsonin Proteins; Thrombosis
PubMed: 36189215
DOI: 10.3389/fimmu.2022.981375 -
Frontiers in Immunology 2018Exosomes are a type of extracellular vesicle whose study has grown exponentially in recent years. This led to the understanding that these structures, far from being... (Review)
Review
Exosomes are a type of extracellular vesicle whose study has grown exponentially in recent years. This led to the understanding that these structures, far from being inert waste by-products of cellular functioning, are active players in intercellular communication mechanisms, including in the interactions between cancer cells and the immune system. The deep comprehension of the crosstalk between tumors and the immune systems of their hosts has gained more and more importance, as immunotherapeutic techniques have emerged as viable options for several types of cancer. In this review, we present a comprehensive, updated, and elucidative review of the current knowledge on the functions played by the exosomes in this crosstalk. The roles of these vesicles in tumor antigen presentation, immune activation, and immunosuppression are approached as the relevant interactions between exosomes and the complement system. The last section of this review is reserved for the exploration of the results from the first phase I to II clinical trials of exosomes-based cell-free cancer vaccines.
Topics: Animals; Antigen Presentation; Complement System Proteins; Exosomes; Humans; Immune Tolerance; Neoplasms; Opsonin Proteins
PubMed: 29696022
DOI: 10.3389/fimmu.2018.00730 -
Autoimmunity Reviews May 2010Systemic lupus erythematosus (SLE) is a complex autoimmune disorder marked by an inappropriate immune response to nuclear antigens. Recent whole genome association and... (Review)
Review
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder marked by an inappropriate immune response to nuclear antigens. Recent whole genome association and more focused studies have revealed numerous genes implicated in this disease process, including ITGAM, Fc gamma receptors, complement components, C-reactive protein, and others. One common feature of these molecules is their involvement in the immune opsonin pathway and in phagocytic clearing of nuclear antigens and apoptotic debris, which provide excessive exposure of lupus-related antigens to immune cells. Analysis of gene-gene interactions in the opsonin pathway and its relationship to SLE may provide a system-based approach to identify additional candidate genes associated with disease able to account for a larger part of lupus susceptibility.
Topics: Animals; Antigen Presentation; Antigens, Nuclear; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Lupus Erythematosus, Systemic; Opsonin Proteins; Phagocytosis; Systems Analysis
PubMed: 20144911
DOI: 10.1016/j.autrev.2010.02.003