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Frontiers in Immunology 2017Human-pathogenic microbes possess various means to avoid destruction by our immune system. These include interactions with the host complement system that may facilitate... (Review)
Review
Human-pathogenic microbes possess various means to avoid destruction by our immune system. These include interactions with the host complement system that may facilitate pathogen entry into cells and tissues, expression of molecules that defuse the effector complement components and complexes, and acquisition of host complement inhibitors to downregulate complement activity on the surface of the pathogen. A growing number of pathogenic microorganisms have acquired the ability to bind the complement inhibitor factor H (FH) from body fluids and thus hijack its host protecting function. In addition to FH, binding of FH-related (FHR) proteins was also demonstrated for several microbes. Initial studies assumed that these proteins are complement inhibitors similar to FH. However, recent evidence suggests that FHR proteins may rather enhance complement activation both directly and also by competing with the inhibitor FH for binding to certain ligands and surfaces. This mini review focuses on the role of the main alternative pathway regulator FH in host-pathogen interactions, as well as on the emerging role of the FHR proteins as enhancers of complement activation.
PubMed: 28572805
DOI: 10.3389/fimmu.2017.00571 -
Expert Opinion on Drug Delivery 2016Nanocomposite microparticles are intelligent carriers utilised for pulmonary drug delivery. These carriers are composed of drug-encapsulated nanoparticles dispersed in... (Review)
Review
INTRODUCTION
Nanocomposite microparticles are intelligent carriers utilised for pulmonary drug delivery. These carriers are composed of drug-encapsulated nanoparticles dispersed in microstructures of polysaccharides. Upon administration, the inhaled microparticles can penetrate and be deposited deeply in the lung due to their adjusted aerodynamic particle size. Subsequently, the nanoparticles are released into the lung and are retained there for a prolonged time due to their resistance to immunological opsonisation, engulfment and digestion.
AREA COVERED
Nanocomposite microparticles may be prepared by spray drying, spray freeze drying, spray drying fluidised bed granulation or dry coating techniques. The selection of the included excipients, preparation technique and optimisation of the operational parameter play a significant role in the determination of the aerodynamic particle size, redispersibility of the nanoparticles, morphology, yield, moisture content, flowability and in vitro drug release. Moreover, the in vivo behaviour of this novel carrier may be optimised and traced by studying the lung deposition of the inhaled particles and the biological activity of the encapsulated drug.
EXPERT OPINION
Nanocomposite microparticles have been found to be superior to both nanoparticles and microparticles and may represent a promising carrier for pulmonary drug delivery.
Topics: Administration, Inhalation; Drug Delivery Systems; Drug-Related Side Effects and Adverse Reactions; Excipients; Freeze Drying; Nanocomposites; Particle Size; Technology, Pharmaceutical
PubMed: 26512950
DOI: 10.1517/17425247.2016.1102224 -
Journal of Fungi (Basel, Switzerland) Feb 2020Antibodies represent an important element in the adaptive immune response and a major tool to eliminate microbial pathogens. For many bacterial and viral infections,... (Review)
Review
Antibodies represent an important element in the adaptive immune response and a major tool to eliminate microbial pathogens. For many bacterial and viral infections, efficient vaccines exist, but not for fungal pathogens. For a long time, antibodies have been assumed to be of minor importance for a successful clearance of fungal infections; however this perception has been challenged by a large number of studies over the last three decades. In this review, we focus on the potential therapeutic and prophylactic use of monoclonal antibodies. Since systemic mycoses normally occur in severely immunocompromised patients, a passive immunization using monoclonal antibodies is a promising approach to directly attack the fungal pathogen and/or to activate and strengthen the residual antifungal immune response in these patients.
PubMed: 32033168
DOI: 10.3390/jof6010022 -
Malaria Journal Jul 2021There are seven known species of Plasmodium spp. that can infect humans. The human host can mount a complex network of immunological responses to fight infection and one... (Review)
Review
There are seven known species of Plasmodium spp. that can infect humans. The human host can mount a complex network of immunological responses to fight infection and one of these immune functions is phagocytosis. Effective and timely phagocytosis of parasites, accompanied by the activation of a regulated inflammatory response, is beneficial for parasite clearance. Functional studies have identified specific opsonins, particularly antibodies and distinct phagocyte sub-populations that are associated with clinical protection against malaria. In addition, cellular and molecular studies have enhanced the understanding of the immunological pathways and outcomes following phagocytosis of malaria parasites. In this review, an integrated view of the factors that can affect phagocytosis of infected erythrocytes and parasite components, the immunological consequences and their association with clinical protection against Plasmodium spp. infection is provided. Several red blood cell disorders and co-infections, and drugs that can influence phagocytic capability during malaria are also discussed. It is hoped that an enhanced understanding of this immunological process can benefit the design of new therapeutics and vaccines to combat this infectious disease.
Topics: Animals; Anopheles; Erythrocytes; Humans; Malaria, Falciparum; Phagocytosis; Plasmodium falciparum
PubMed: 34271941
DOI: 10.1186/s12936-021-03849-1 -
Parasite Immunology Aug 2020The parasitic ciliate Ichthyophthirius multifiliis causes white spot disease in freshwater fish worldwide. The theront penetrates external surfaces of the naïve fish... (Review)
Review
The parasitic ciliate Ichthyophthirius multifiliis causes white spot disease in freshwater fish worldwide. The theront penetrates external surfaces of the naïve fish where it develops into the feeding trophont stage and elicits a protective immune response both at the affected site as well as at the systemic level. The present work compiles data and presents an overall model of the protective reactions induced. A wide spectrum of inflammatory reactions are established upon invasion but the specific protection is provided by adaptive factors. Immunoglobulin IgT is involved in protection of surfaces in several fish species and is thereby one of the first adaptive immune molecules reacting with the penetrating theront. IgT producing lymphocytes occur in epithelia, dispersed or associated with lymphoid cell aggregations (skin epidermis, fins, gills, nostrils and buccal cavities) but they are also present in central immune organs such as the head kidney, spleen and liver. When theronts invade immunized fish skin, they are encountered by host factors which opsonize the parasite and may result in complement activation, phagocytosis or cell-mediated killing. However, antibody (IgT, IgM and IgD) binding to parasite cilia has been suggested to alter parasite behaviour and induce an escape reaction, whereby specific IgT (or other classes of immunoglobulin in fish surfaces) takes a central role in protection against the parasite.
Topics: Animals; Antibodies, Protozoan; Ciliophora Infections; Fish Diseases; Fish Proteins; Fishes; Gills; Hymenostomatida; Immunization; Immunoglobulins; Spleen
PubMed: 31587318
DOI: 10.1111/pim.12675 -
Viruses May 2021The complement system represents a crucial part of innate immunity. It contains a diverse range of soluble activators, membrane-bound receptors, and regulators. Its... (Review)
Review
The complement system represents a crucial part of innate immunity. It contains a diverse range of soluble activators, membrane-bound receptors, and regulators. Its principal function is to eliminate pathogens via activation of three distinct pathways: classical, alternative, and lectin. In the case of viruses, the complement activation results in effector functions such as virion opsonisation by complement components, phagocytosis induction, virolysis by the membrane attack complex, and promotion of immune responses through anaphylatoxins and chemotactic factors. Recent studies have shown that the addition of individual complement components can neutralise viruses without requiring the activation of the complement cascade. While the complement-mediated effector functions can neutralise a diverse range of viruses, numerous viruses have evolved mechanisms to subvert complement recognition/activation by encoding several proteins that inhibit the complement system, contributing to viral survival and pathogenesis. This review focuses on these complement-dependent and -independent interactions of complement components (especially C1q, C4b-binding protein, properdin, factor H, Mannose-binding lectin, and Ficolins) with several viruses and their consequences.
Topics: Complement Activation; Complement System Proteins; Cytokine Release Syndrome; Cytopathogenic Effect, Viral; Humans; Immunity, Innate; Receptors, Pattern Recognition; Viruses
PubMed: 34063241
DOI: 10.3390/v13050824 -
Infection and Immunity Jun 2020The human respiratory tract pathogen , which causes mild to severe infections, has been associated with the development of chronic inflammatory diseases. To understand...
The human respiratory tract pathogen , which causes mild to severe infections, has been associated with the development of chronic inflammatory diseases. To understand the biology of infections, several studies have investigated the interaction between and professional phagocytes. However, these studies have been conducted under nonopsonizing conditions, making the role of opsonization in infections elusive. Thus, we analyzed complement and antibody opsonization of and evaluated how opsonization affects chlamydial infectivity and phagocytosis in human monocytes and neutrophils. We demonstrated that IgG antibodies and activation products of complement C3 and C4 are deposited on the surface of elementary bodies when incubated in human serum. Complement activation limits infectivity and has the potential to induce bacterial lysis by the formation of the membrane attack complex. Coculture of and freshly isolated human leukocytes showed that complement opsonization is superior to IgG opsonization for efficient opsonophagocytosis of in monocytes and neutrophils. Neutrophil-mediated phagocytosis of was crucially dependent on opsonization, while monocytes retained minor phagocytic potential under nonopsonizing conditions. Complement opsonization significantly enhanced the intracellular neutralization of in peripheral blood mononuclear cells and neutrophils and almost abrogated the infectious potential of In conclusion, we demonstrated that complements limit infection by interfering with entry into permissive cells by direct complement-induced lysis and by tagging bacteria for efficient phagocytosis in both monocytes and neutrophils.
Topics: Antibodies, Bacterial; Chlamydophila Infections; Chlamydophila pneumoniae; Complement Activation; Complement System Proteins; Humans; Monocytes; Neutrophils; Phagocytosis
PubMed: 32284372
DOI: 10.1128/IAI.00087-20 -
Nanoscale Horizons Mar 2019To maximize drug targeting to solid tumors, cancer nanomedicines with prolonged circulation times are required. To this end, poly(ethylene glycol) (PEG) has been widely... (Review)
Review
To maximize drug targeting to solid tumors, cancer nanomedicines with prolonged circulation times are required. To this end, poly(ethylene glycol) (PEG) has been widely used as a steric shield of nanomedicine surfaces to minimize serum protein absorption (opsonisation) and subsequent recognition and clearance by cells of the mononuclear phagocyte system (MPS). However, PEG also inhibits interactions of nanomedicines with target cancer cells, limiting the effective drug dose that can be reached within the target tumor. To overcome this dilemma, nanomedicines with stimuli-responsive cleavable PEG functionality have been developed. These benefit from both long circulation lifetimes en route to the targeted tumor as well as efficient drug delivery to target cancer cells. In this review, various stimuli-responsive strategies to dePEGylate nanomedicines within the tumor microenvironment will be critically reviewed.
Topics: Animals; Antineoplastic Agents; Drug Carriers; Drug Delivery Systems; Humans; Nanomedicine; Nanoparticles; Neoplasms; Polyethylene Glycols; Tumor Microenvironment
PubMed: 32254090
DOI: 10.1039/c8nh00417j -
Experimental Biology and Medicine... Feb 2017The complement system is one of the body's major innate immune defense mechanisms in vertebrates. Its function is to detect foreign bodies and promote their elimination... (Review)
Review
The complement system is one of the body's major innate immune defense mechanisms in vertebrates. Its function is to detect foreign bodies and promote their elimination through opsonisation or lysis. Complement proteins play an important role in the immunopathogenesis of several disorders. However, excessive complement activation does not confer more protection but instead leads to several autoimmune and inflammatory diseases. With inappropriate activation of the complement system, activated complement proteins and glycoproteins may damage both healthy and diseased tissues. Development of complement inhibitors represents an effective approach in controlling dysregulated complement activity and reducing disease severity, yet few studies have investigated the nature and role of novel complement inhibitory proteins of viral origin. Viral complement inhibitors have important implications in understanding the importance of complement inhibition and their role as a promising novel therapeutic approach in diseases caused by dysregulated complement function. In this review, we discuss the role and importance of complement inhibitors derived from several viruses in the scope of human inflammatory and autoimmune diseases.
Topics: Animals; Autoimmune Diseases; Complement Activation; Complement Inactivating Agents; Complement System Proteins; Humans; Immunomodulation; Inflammation; Mice; Viral Proteins; Virus Diseases; Viruses
PubMed: 27798122
DOI: 10.1177/1535370216675772 -
Proceedings of the National Academy of... Jan 2022Gram-positive organisms with their thick envelope cannot be lysed by complement alone. Nonetheless, antibody-binding on the surface can recruit complement and mark these...
Gram-positive organisms with their thick envelope cannot be lysed by complement alone. Nonetheless, antibody-binding on the surface can recruit complement and mark these invaders for uptake and killing by phagocytes, a process known as opsonophagocytosis. The crystallizable fragment of immunoglobulins (Fcγ) is key for complement recruitment. The cell surface of is coated with Staphylococcal protein A (SpA). SpA captures the Fcγ domain of IgG and interferes with opsonization by anti- antibodies. In principle, the Fcγ domain of therapeutic antibodies could be engineered to avoid the inhibitory activity of SpA. However, the SpA-binding site on Fcγ overlaps with that of the neonatal Fc receptor (FcRn), an interaction that is critical for prolonging the half-life of serum IgG. This evolutionary adaptation poses a challenge for the exploration of Fcγ mutants that can both weaken SpA-IgG interactions and retain stability. Here, we use both wild-type and transgenic human FcRn mice to identify antibodies with enhanced half-life and increased opsonophagocytic killing in models of infection and demonstrate that antibody-based immunotherapy can be improved by modifying Fcγ. Our experiments also show that by competing for FcRn-binding, staphylococci effectively reduce the half-life of antibodies during infection. These observations may have profound impact in treating cancer, autoimmune, and asthma patients colonized or infected with and undergoing monoclonal antibody treatment.
Topics: Amino Acid Sequence; Antibodies, Bacterial; Antibodies, Monoclonal; Antibody-Dependent Cell Cytotoxicity; Complement Activation; Dose-Response Relationship, Drug; Dose-Response Relationship, Immunologic; Humans; Opsonization; Phagocytosis; Protein Binding; Protein Engineering; Protein Interaction Domains and Motifs; Receptors, Fc; Staphylococcal Protein A; Staphylococcus aureus
PubMed: 35058363
DOI: 10.1073/pnas.2114478119