The existence of pattern recognition receptors (PRRs) on immune cells was discussed in 1989 by Charles Janeway, Jr., who proposed a general concept of the ability of PRRs to recognize and bind conserved molecular structures of microorganisms known as pathogen-associated molecular patterns (PAMPs). Upon PAMP engagement, PRRs trigger intracellular signaling cascades resulting in the expression of various proinflammatory molecules. These recognition molecules represent an important and efficient innate immunity tool of all organisms. As invertebrates lack the instruments of the adaptive immune system, based on "true" lymphocytes and functional antibodies, the importance of PRRs are even more fundamental. In the present review, the structure, specificity, and expression profiles of PRRs characterized in annelids are discussed, and their role in innate defense is suggested.
- MeSH
- Annelida immunology MeSH
- Membrane Glycoproteins chemistry genetics metabolism MeSH
- Pathogen-Associated Molecular Pattern Molecules immunology metabolism MeSH
- Immunity, Innate * MeSH
- Acute-Phase Proteins chemistry genetics metabolism MeSH
- Receptors, Pattern Recognition chemistry genetics metabolism MeSH
- Gene Expression Regulation MeSH
- Signal Transduction immunology MeSH
- Tissue Distribution MeSH
- Toll-Like Receptors chemistry genetics metabolism MeSH
- Carrier Proteins chemistry genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Imunitní systém je součástí komplexních tělních mechanizmů, zánětu, kterými člověk reaguje na expozici patogenním mikroorganizmům nebo poškození vlastních struktur. Především složky vrozené imunity jsou vybaveny receptory, kterými identifikují vzory patogenů PAMP a signály vnitřního poškození DAMP. Charakteristika zánětlivé odpovědi je určena aktuálními potřebami. Potenciál zánětlivé reakce je velký a jeho intenzita i rozsah musí být přísně regulovány na mnoha úrovních.
Immune system is the integral part of the complex body response, inflammation, which is raised either by the exposure to external signals, predominantly pathogens or by damage of own structures. Predominantly innate immunity is equiped by the receptors recognizing pathogenic PAMPs or signals of own damage DAMPs. The inflammatory response is reflecting the actual demand of our body. The potential of the inflammatory response is so powerful that its intensity and extent have to be carefully regulated on many levels.
Coelomic fluid of the Lumbricid Eisenia fetida contains a 42-kDa pattern recognition protein named coelomic cytolytic factor (CCF) that binds microbial cell wall components and triggers the activation of the prophenoloxidase cascade, an important invertebrate defense pathway. Here we report on the sequence characterization of CCF-like molecules of other Lumbricids: Aporrectodea caliginosa, Aporrectodea icterica, Aporrectodea longa, Aporrectodea rosea, Dendrobaena veneta, Lumbricus rubellus and Lumbricus terrestris, and show that CCF from E. fetida has a broader saccharide-binding specificity, being the only one recognizing N,N'-diacetylchitobiose. We suggest that the broad recognition repertoire of E. fetida CCF reflects a particular microbial environment this species lives in.
- MeSH
- Cytotoxins pharmacology genetics metabolism MeSH
- Disaccharides metabolism MeSH
- Financing, Organized MeSH
- Phylogeny MeSH
- Catechol Oxidase metabolism MeSH
- Lectins pharmacology genetics metabolism MeSH
- Humans MeSH
- Molecular Sequence Data MeSH
- Cell Line, Tumor MeSH
- Oligochaeta genetics metabolism MeSH
- Enzyme Precursors metabolism MeSH
- Amino Acid Sequence MeSH
- Base Sequence MeSH
- Sequence Alignment MeSH
- Substrate Specificity MeSH
- Random Amplified Polymorphic DNA Technique MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Comparative Study MeSH
Primary interaction of an intracellular bacterium with its host cell is initiated by activation of multiple signaling pathways in response to bacterium recognition itself or as cellular responses to stress induced by the bacterium. The leading molecules in these processes are cell surface membrane receptors as well as cytosolic pattern recognition receptors recognizing pathogen-associated molecular patterns or damage-associated molecular patterns induced by the invading bacterium. In this review, we demonstrate possible sequences of events leading to recognition of Francisella tularensis, present findings on known mechanisms for manipulating cell responses to protect Francisella from being killed, and discuss newly published data from the perspective of early stages of host-pathogen interaction.
- MeSH
- Alarmins genetics immunology MeSH
- Bacterial Proteins genetics immunology MeSH
- Phagocytosis genetics MeSH
- Francisella tularensis genetics immunology pathogenicity MeSH
- Host-Pathogen Interactions genetics immunology MeSH
- Humans MeSH
- Macrophages immunology microbiology MeSH
- Pathogen-Associated Molecular Pattern Molecules immunology metabolism MeSH
- Immunity, Innate * MeSH
- Receptors, Cell Surface genetics immunology MeSH
- Receptors, Pattern Recognition genetics immunology MeSH
- Gene Expression Regulation MeSH
- Signal Transduction MeSH
- Tularemia genetics immunology microbiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Imunitní systém je v kooperaci s neuroendokrinní soustavou odpovědný za udržování homeostázy. Podněty, které vedou k narušení homeostázy, jsou označovány jako nebezpečné. Tělo je identifikuje prostřednictvím receptorů PRR s následnou zánětovou odpovědí. Buňky vrozené imunity (dendritické buňky) zpracovávají nebezpečné vzory a z nich vzniklé antigenní fragmenty navázané na molekuly HLA-I, II předkládají T lymfocytům. T lymfocyty proliferují a vykazují efektorové funkce. Zánětová odpověď je na řadě úrovní regulována tak, aby imunitní odpověď byla realizována efektivně s minimálními negativními dopady na organizmus.
The immune system, together with the neuroendocrine system, is responsible for the maintenance of homeostasis. Signals which disturb homeostasis are recognized as danger signals by PRR receptors with subsequent development of the inflammatory response. Innate immunity cells (dendritic cells) process danger molecules. Antigenic fragments from danger molecules are presented to T cells in the context of HLA-I,II molecules. T cells proliferate following antigenic stimulation, displaying numerous effector and regulatory functions. The inflammatory response is carefully regulated on numerous levels to achieve protective immunity without harmful effects on the organism.
- Keywords
- imunitní odpověď, regulace,
- MeSH
- Cytokines blood MeSH
- Financing, Organized MeSH
- Immune System Phenomena physiology immunology MeSH
- Humans MeSH
- Receptors, Pattern Recognition immunology MeSH
- T-Lymphocytes, Regulatory immunology MeSH
- Inflammation immunology blood MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
The tube-within-tube body plan of earthworms is appropriate for studying the interactions of microorganisms with the immune system of body cavities such as the digestive tract and coelom. This study aims to describe the immune response on the molecular and cellular level in the coelomic cavity and the gut of the earthworm Eisenia andrei after experimental microbial challenge by administering two bacterial strains (Escherichia coli and Bacillus subtilis) or yeast Saccharomyces cerevisiae to the environment. The changes in mRNA levels of defense molecules (pattern recognition receptor CCF, lysozyme, fetidin/lysenins) in the coelomocytes and gut tissue were determined by quantitative PCR. The immune response at a cellular level was captured in histological sections, and the expression of CCF was localized using in situ hybridization. Coelomocytes respond to the presence of bacteria in the coelomic cavity by increasing the mRNA levels of defense molecules, especially CCF. The immune response in gut tissue is less affected by microbial stimulation because the epithelial cells of gut exhibit basically strong mRNA synthesis of ccf as a defense against the continuous microbial load in the gut lumen. The cellular immune response is mediated by coelomocytes released from the mesenchymal lining of the coelomic cavity. These combined immune mechanisms are necessary for the survival of earthworms in the microbially rich environment of soil.
- MeSH
- Bacillus subtilis immunology MeSH
- Immunity, Cellular MeSH
- Escherichia coli immunology MeSH
- Gram-Negative Bacterial Infections immunology MeSH
- Gram-Positive Bacterial Infections immunology MeSH
- Lectins genetics metabolism MeSH
- Mesoderm immunology pathology MeSH
- Mycoses immunology MeSH
- Oligochaeta immunology MeSH
- Receptors, Pattern Recognition genetics metabolism MeSH
- Saccharomyces immunology MeSH
- Immunity, Mucosal MeSH
- Intestinal Mucosa immunology microbiology virology MeSH
- Up-Regulation MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The Fox-1 RNA recognition motif (RRM) domain is an important member of the RRM protein family. We report a 1.8 Å X-ray structure of the free Fox-1 containing six distinct monomers. We use this and the nuclear magnetic resonance (NMR) structure of the Fox-1 protein/RNA complex for molecular dynamics (MD) analyses of the structured hydration. The individual monomers of the X-ray structure show diverse hydration patterns, however, MD excellently reproduces the most occupied hydration sites. Simulations of the protein/RNA complex show hydration consistent with the isolated protein complemented by hydration sites specific to the protein/RNA interface. MD predicts intricate hydration sites with water-binding times extending up to hundreds of nanoseconds. We characterize two of them using NMR spectroscopy, RNA binding with switchSENSE and free-energy calculations of mutant proteins. Both hydration sites are experimentally confirmed and their abolishment reduces the binding free-energy. A quantitative agreement between theory and experiment is achieved for the S155A substitution but not for the S122A mutant. The S155 hydration site is evolutionarily conserved within the RRM domains. In conclusion, MD is an effective tool for predicting and interpreting the hydration patterns of protein/RNA complexes. Hydration is not easily detectable in NMR experiments but can affect stability of protein/RNA complexes.
- MeSH
- Crystallography, X-Ray MeSH
- Humans MeSH
- RNA Recognition Motif genetics MeSH
- Mutagenesis, Site-Directed MeSH
- Nuclear Magnetic Resonance, Biomolecular MeSH
- Recombinant Proteins chemistry genetics metabolism MeSH
- RNA metabolism MeSH
- RNA Splicing Factors chemistry genetics metabolism MeSH
- Molecular Dynamics Simulation MeSH
- Amino Acid Substitution MeSH
- Binding Sites MeSH
- Water chemistry MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Red blood cells (RBCs), also known as erythrocytes, are underestimated in their role in the immune system. In mammals, erythrocytes undergo maturation that involves the loss of nuclei, resulting in limited transcription and protein synthesis capabilities. However, the nucleated nature of non-mammalian RBCs is challenging this conventional understanding of RBCs. Notably, in bony fishes, research indicates that RBCs are not only susceptible to pathogen attacks but express immune receptors and effector molecules. However, given the abundance of RBCs and their interaction with every physiological system, we postulate that they act in surveillance as sentinels, rapid responders, and messengers. METHODS: We performed a series of in vitro experiments with Cyprinus carpio RBCs exposed to Aeromonas hydrophila, as well as in vivo laboratory infections using different concentrations of bacteria. RESULTS: qPCR revealed that RBCs express genes of several inflammatory cytokines. Using cyprinid-specific antibodies, we confirmed that RBCs secreted tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). In contrast to these indirect immune mechanisms, we observed that RBCs produce reactive oxygen species and, through transmission electron and confocal microscopy, that RBCs can engulf particles. Finally, RBCs expressed and upregulated several putative toll-like receptors, including tlr4 and tlr9, in response to A. hydrophila infection in vivo. DISCUSSION: Overall, the RBC repertoire of pattern recognition receptors, their secretion of effector molecules, and their swift response make them immune sentinels capable of rapidly detecting and signaling the presence of foreign pathogens. By studying the interaction between a bacterium and erythrocytes, we provide novel insights into how the latter may contribute to overall innate and adaptive immune responses of teleost fishes.
- MeSH
- Aeromonas hydrophila * immunology MeSH
- Cytokines * metabolism immunology MeSH
- Erythrocytes * immunology metabolism MeSH
- Phagocytosis immunology MeSH
- Gram-Negative Bacterial Infections * immunology MeSH
- Carps * immunology microbiology MeSH
- Fish Diseases * immunology microbiology MeSH
- Pathogen-Associated Molecular Pattern Molecules immunology MeSH
- Immunity, Innate MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
Recognition of pathogen-associated molecular patterns (PAMPs) is crucial for plant defence against pathogen attack. The best characterized PAMP is flg22, a 22 amino acid conserved peptide from flagellin protein. In Arabidopsis thaliana, flg22 is recognized by the flagellin sensing 2 (FLS2) receptor. In this study, we focused on biotic stress responses triggered by flg22 after exposure to temporary heat stress (HS). It is important to study the reactions of plants to multiple stress conditions because plants are often exposed simultaneously to a combination of both abiotic and biotic stresses. Transient early production of reactive oxygen species (ROS) is a well-characterized response to PAMP recognition. We demonstrate the strong reduction of flg22-induced ROS production in A. thaliana after HS treatment. In addition, a decrease in FLS2 transcription and a decrease of the FLS2 presence at the plasma membrane are shown after HS. In summary, our data show the strong inhibitory effect of HS on flg22-triggered events in A. thaliana. Subsequently, temporary HS strongly decreases the resistance of A. thaliana to Pseudomonas syringae. We propose that short exposure to high temperature is a crucial abiotic stress factor that suppresses PAMP-triggered immunity, which subsequently leads to the higher susceptibility of plants to pathogens.
- MeSH
- Alarmins metabolism MeSH
- Arabidopsis drug effects genetics immunology microbiology MeSH
- Flagellin pharmacology MeSH
- Transcription, Genetic drug effects MeSH
- Plant Immunity * drug effects MeSH
- Plant Diseases immunology microbiology MeSH
- Disease Resistance immunology MeSH
- Arabidopsis Proteins genetics metabolism MeSH
- Pseudomonas syringae drug effects physiology MeSH
- Heat-Shock Response * drug effects MeSH
- Gene Expression Regulation, Plant drug effects MeSH
- Respiratory Burst drug effects MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
β-glucans are cell wall constituents of bacteria, yeast, fungi, and plants. They are not expressed in mammalian cells, but they are recognized by mammalian cells as pathogen-associated molecular patterns by pattern recognition receptors and thus act as biological response modifiers. This review summarizes data on the hematopoiesis-stimulating effects of β-glucans, as well as on their ability to enhance bone marrow recovery after an injury. β-glucans have been shown to support murine hematopoiesis suppressed by ionizing radiation or cytotoxic anti-cancer therapy. They also enhance stem cell homing and engraftment. Basically, two forms of β-glucan preparations have been investigated, namely particulate and soluble ones. β-glucans are generally well tolerated, the particulate forms showing a higher incidence of undesirable side effects. Taken together, the hematopoiesis-stimulating properties of β-glucans predetermine these biological response modifiers to ever increasing use in human medicinal practice.
- MeSH
- Anemia chemically induced drug therapy MeSH
- beta-Glucans adverse effects pharmacology therapeutic use MeSH
- Hematinics adverse effects pharmacology therapeutic use MeSH
- Hematopoiesis drug effects radiation effects MeSH
- Dosage Forms MeSH
- Humans MeSH
- Antineoplastic Agents adverse effects MeSH
- Radiotherapy adverse effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
