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Results for “Innate Immunity Recognition”

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PubMed2006

Diversity in lectins enables immune recognition and differentiation of wide spectrum of pathogens.

Carbohydrate-binding lectins play essential roles as pattern recognition receptors in innate immunity in both vertebrates and invertebrates. The carcinolectins 5 (CL5a and CL5b, the CL5 isoforms of horseshoe crab, Carcinoscorpius rotundicauda, with apparent sizes of 36 and 40 kDa, respectively) are prominent plasma lectins that bind all representative microbes and pathogen-associated molecular pattern molecules. Different cDNA isoforms of both CL5a and CL5b were isolated, leading to our speculation on their functional divergence. Characterization of CL5 isoforms bound to microbial cell surfaces demonstrates the diversity of these lectins. The resolution patterns of the isoforms that associate with fungus differ from those that associate with bacteria, suggesting the unique roles these lectins play in the recognition and differentiation of microbes. We postulate that different populations of plasma lectins act in collaboration in frontline innate immune defense against disparate pathogens. The functional diversity of lectins in invertebrates appears to evolutionarily compensate for the lack of acquired immunity.

Amino Acid Sequence↗
PubMed2006

[Intra- and extracellular recognition of pathogens and activation of innate immunity].

One of the fundamental questions in innate immunity is how a large battery of invading pathogens is recognized by a limited number of germ line-encoding receptors. In Drosophila, peptidoglycan recognition protein (PGRP) family members have a crucial role in recognizing invading bacterial pathogens and in inducing immune reactions. PGRP-SA, -SD, and -SC1a are involved in recognizing gram-positive bacteria and in activating the Toll pathway to produce antimicrobial peptides. PGRP-LC and -LE recognize diaminopimelic acid (DAP)-containing peptidoglycans, which are cell wall components of many gram-negative bacteria and some gram-positive bacteria, and activate the imd pathway to produce antibacterial peptides. In addition to the extracellular function of PGRP-LE to activate immune reactions in the hemolymph, PGRP-LE acts as an intracellular receptor for monomeric DAP-type peptidoglycans. Moreover, a version of PGRP-LE containing only the PGRP domain functions extracellularly as a CD14-like accessory factor, capable of enhancing PGRP-LC-mediated peptidoglycan recognition. Subsequent intracellular signaling is transduced through the RHIM-like motif found in PGRP-LC and -LE.

Animals↗
PubMed2005

Strain-specific mycobacterial lipids and the stimulation of protective immunity to tuberculosis.

Control of Mycobacterium tuberculosis (M. tuberculosis) infection is dependent on recognition of bacilli by cells of the innate immune system in the lung and the subsequent generation of an acquired effector T lymphocyte response. Lipid moieties of M. tuberculosis are important stimulators of innate immunity mediated predominantly through recognition by Toll-like receptors. In this paper, we will discuss how the lipid composition of different clinical isolates (strains) of M. tuberculosis affect that strain's ability to direct innate immunity, and ultimately influence whether infection is controlled or active disease develops.

Antigen Presentation↗
PubMed2004

The innate immune response in the central nervous system and its role in glioma immune surveillance.

The innate immune system encompasses natural killer (NK) cells, macrophages and granulocytes, the complement system and antimicrobial peptides. Recognition pathways of the innate immune system include microbial non-self recognition, missing-self recognition and induced- self recognition. The central nervous system (CNS) participates in responses of the innate immune system. However, immune inhibitory and anti-inflammatory mechanisms physiologically outbalance and counteract immune activity and thereby limit immune-mediated tissue damage in the brain. Human gliomas appear to take advantage of this immunosuppressive milieu. Moreover, glioma cells themselves interfere with anti-tumor immune responses by expressing immune inhibitory cell surface molecules, such as HLA-G, or by releasing soluble immunosuppressants such as transforming growth factor (TGF)-beta. Yet, although glioma cells exhibit all cellular features of malignancy, these tumors very rarely metastasize outside the brain, raising the possibility of immune-mediated control of these cells outside, but not inside, the brain. Accordingly, activating the innate immune system by forcing glioma cells to express danger signals such as NKG2D ligands is a promising strategy of immunotherapy for these tumors.

Animals↗
PubMed2004

Toll-like receptor 2 plays a role in the early inflammatory response to murine pneumococcal pneumonia but does not contribute to antibacterial defense.

Toll-like receptors (TLR) are crucial pattern recognition receptors in innate immunity. The importance of TLR2 in host defense against Gram-positive bacteria has been suggested by the fact that this receptor recognizes major Gram-positive cell wall components, such as peptidoglycan and lipoteichoic acid. To determine the role of TLR2 in pulmonary Gram-positive infection, we first established that TLR2 is indispensable for alveolar macrophage responsiveness toward Streptococcus pneumoniae. Nonetheless, TLR2 gene-deficient mice intranasally inoculated with S. pneumoniae at doses varying from nonlethal (with complete clearance of the infection) to lethal displayed only a modestly reduced inflammatory response in their lungs and an unaltered antibacterial defense when compared with normal wild-type mice. These data suggest that TLR2 plays a limited role in the innate immune response to pneumococcal pneumonia, and that additional pattern recognition receptors likely are involved in host defense against this common respiratory pathogen.

Animals↗
PubMed2005

Differential gene expression of IGF-I, IGF-II, and toll-like receptors 3 and 5 during embryogenesis in hybrid (channel x blue) and channel catfish.

Insulin-like growth factors-I and-II (IGF-I and IGF-II) play important roles in growth and development of mammals. Toll-like receptors (TLRs) are pattern recognition molecules that orchestrate the induction of early innate immune response by recognition of specific sequences. Evidence is growing that suggests a relationship between growth and immune function. The objective of the study was to examine changes in gene expression of IGF-I, IGF-II, TLR3, and TLR5 during embryogenesis and early larval development in hybrid (channel catfishxblue catfish) and channel catfish. Egg samples were taken pre- and post-fertilization; embryos were collected at two stages of embryogenesis, at hatch, and at swim-up. All genes were detected in unfertilized catfish eggs. Expression levels of TLR5 and IGF-I mRNA in channel catfish and expression levels of TLR3, IGF-I, and IGF-II mRNA in hybrids increased over time (P<0.01). Effect of time was not significant for expression of IGF-II or TLR3 mRNA in channel catfish and for TLR5 mRNA in hybrid catfish. Results of this study suggest growth (IGF-I and IGF-II) and immune (TLR3 and TLR5) associated genes could be functional and play important roles during embryogenesis and early development of hybrid and channel catfish.

Animals↗
PubMed2005

Dendritic cell maturation by innate lymphocytes: coordinated stimulation of innate and adaptive immunity.

Pathogen recognition by Toll-like receptors (TLRs) on dendritic cells (DCs) leads to DC maturation and the initiation of adaptive immunity. Recent studies have shown that innate lymphocytes--natural killer (NK), natural killer T (NKT), and gammadelta T cells--also trigger DC maturation. This interaction in turn expands and activates innate lymphocytes and initiates adaptive T cell immunity. Here, we comment on the evidence that these pathways are TLR independent and have the potential to respond to infection, malignancy, and immunotherapy.

Animals↗
PubMed2002

Introduction: innate recognition of bacteria and protozoan parasites.

Major advances have recently been achieved in the area of microbial recognition by the innate immune system. In this Forum, we discuss important issues related to innate recognition of bacteria and protozoan parasites. In particular, we highlight the structural characterization of pathogen-associated molecular patterns (PAMPs); the definition of the receptors required for recognition of PAMPs, especially the Toll-like receptors (TLRs); the signaling pathways triggered by PAMPs/PAMPs receptor interaction; and the functional consequences of these interactions for pathogenesis during microbial infection.

Animals↗
PubMed2004

Pathogen recognition or homeostasis? APC receptor functions in innate immunity.

Myeloid cells (macrophages, neutrophils, dendritic cells) express a repertoire of plasma membrane receptors able to recognize all classes of macromolecules. The concept of pattern recognition has emphasized microbial ligands and host defence. However, these receptors play a broader role in tissue homeostasis within multicellular hosts, clearing the extracellular environment of potential undesirable ligands arising endogenously as well as from without. This article will evaluate one of the paradigms that underlie innate immunity.

Animals↗
PubMed2006

Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor gamma chain to induce innate immune responses.

Antigen presenting cells recognize pathogens via pattern recognition receptors (PRR), which upon ligation transduce intracellular signals that can induce innate immune responses. Because some C-type lectin-like receptors (e.g. dectin-1 and DCSIGN) were shown to act as PRR for particular microbes, we considered a similar role for dectin-2. Binding assays using soluble dectin-2 receptors showed the extracellular domain to bind preferentially to hyphal (rather than yeast/conidial) components of Candida albicans, Microsporum audouinii, and Trichophyton rubrum. Selective binding for hyphae was also observed using RAW macrophages expressing dectin-2, the ligation of which by hyphae or cross-linking with dectin-2-specific antibody led to protein tyrosine phosphorylation. Because dectin-2 lacks an intracellular signaling motif, we searched for a signal adaptor that permits it to transduce intracellular signals. First, we found that the Fc receptor gamma (FcRgamma) chain can bind to dectin-2. Second, ligation of dectin-2 on RAW cells induced tyrosine phosphorylation of FcRgamma, activation of NF-kappaB, internalization of a surrogate ligand, and up-regulated secretion of tumor necrosis factor alpha and interleukin-1 receptor antagonist. Finally, these dectin-2-induced events were blocked by PP2, an inhibitor of Src kinases that are mediators for FcRgamma chain-dependent signaling. We conclude that dectin-2 is a PRR for fungi that employs signaling through FcRgamma to induce innate immune responses.

Animals↗
PubMed2006

Pathogen recognition and signalling in the Drosophila innate immune response.

Genetic analysis of the innate immune response in Drosophila has provided important insights into the mechanism of microbial sensing and the subsequent host signalling events. The two major players following immune challenge are the Toll and Immune deficiency (IMD) pathways, which are essential for fruit flies to survive infection. These pathways are homologous to the mammalian Toll-like receptor and tumour necrosis factor pathways, respectively. Moreover, microbial pattern-recognition receptors upstream of Toll and IMD, such as the peptidoglycan recognition proteins, have been isolated and studied at the structural and functional level. In the present, we will review recent data pertaining to the genetic, genomic, RNAi and infection studies that have added new complexities to the system.

Animals↗
PubMed2002

Innate immunity and its role against infections.

LEARNING OBJECTIVES: This article reviews current concepts of the innate immune system that offers protection against infections. It offers an overview for the readers to understand how innate immunity, consisting of different receptors, cells, and mediators recognizes pathogens and exerts protective function against pathogens. DATA SOURCES AND STUDY SELECTION: MEDLINE-search articles including original research papers, review articles, textbooks, and references identified from bibliographies of relevant articles. RESULTS AND CONCLUSIONS: The innate immune system is nonspecific immunity present since birth not requiring repeated exposure to pathogens. It is capable of differentiation between self and nonself. Because of its nonspecificity, it has a broad spectrum of resistance to infection. Further, it is thought to play an important role in the control of adaptive immunity by regulating co-stimulatory molecules and effector cytokines. Innate immunity includes pattern recognition molecules/receptors, antimicrobial peptides, the complement system, inflammatory mediators, and cytokines produced by immune cells. Pattern recognition molecules/receptors recognize pathogen-associated molecular patterns that are essential for microorganisms' survival and pathogenicity. Although innate immunity has recently gained increasing importance, further studies are necessary for a better understanding of its role.

Animals↗
PubMed1998

Bacterial DNA as an evolutionary conserved ligand signalling danger of infection to immune cells.

During infection, the innate limb of the immune system senses danger (pathogens) via constitutively expressed pattern-recognition receptors, and responds with activation and secretion of pro-inflammatory cytokines. Cell-wall components of gram-positive and gram-negative bacteria, such as peptidoglycan, endotoxin or lipoteichoic acid, activate via CD14, a prototypic pattern-recognition receptor for carbohydrates. This review article focuses on an alternative recognition system of the innate immune system for the recognition of bacterial DNA. Bacterial DNA differs from eukaryotic DNA in its frequency of the dinucleotides CG and its lack of methylation. These structural differences appear to be sensed by cells of the innate immune system such as antigen-presenting cells. As a consequence bacterial DNA serves as an alternate ligand to signal danger of infection. Bacterial DNA and (synthetic) oligonucleotides (ODN) derived thereof are as efficient as endotoxin in activating macrophages and dendritic cells and in triggering release of pro-inflammatory cytokines. In mice sensitized with D-galactosamine (D-GalN), high doses of bacterial DNA from either gram-positive or gram-negative pathogens induce a lethal cytokine syndrome (lethal shock). Therefore, bacterial DNA may represent a hitherto unrecognized pathophysiological entity in host-parasite interactions. Moreover, recent evidence suggests that bacterial DNA or immunostimulating ODN triggers the immunostimulation of antigen-presenting cells, and can be utilized as adjuvant to enhance immune responses of the adaptive immune system towards poorly immunogenic antigens. In fact, foreign DNA might be useful as immunotherapeutically active adjuvant to direct adaptive immune responses towards Thl-dominated immune reactions. If these findings are operative in humans, immunostimulating ODN might be used to influence Th2-dominated diseases such as allergy.

Animals↗
PubMed2001

Recognition of tumor cells by the innate immune system.

There has been a rapid increase in our understanding of the cellular components of the innate immune system, the receptors used to distinguish changes in homeostasis, and how these components integrate into an anti-tumor effector response. Recently, significant progress has been made in the identification of ligands for receptors that activate NK cells, and the results have implications for the recognition of tumor cells.

Adaptor Proteins, Signal Transducing↗
PubMed2004

C1q and tumor necrosis factor superfamily: modularity and versatility.

C1q is the target recognition protein of the classical complement pathway and a major connecting link between innate and acquired immunity. As a charge pattern recognition molecule of innate immunity, C1q can engage a broad range of ligands via its globular (gC1q) domain and modulate immune cells, probably via its collagen region. The gC1q signature domain, also found in many non-complement proteins, has a compact jelly-roll beta-sandwich fold similar to that of the multifunctional tumor necrosis factor (TNF) ligand family. The members of this newly designated 'C1q and TNF superfamily' are involved in processes as diverse as host defense, inflammation, apoptosis, autoimmunity, cell differentiation, organogenesis, hibernation and insulin-resistant obesity. This review is an attempt to draw structural and functional parallels between the members of the C1q and TNF superfamily.

Amino Acid Sequence↗
PubMed2002

MAP kinase signalling cascade in Arabidopsis innate immunity.

There is remarkable conservation in the recognition of pathogen-associated molecular patterns (PAMPs) by innate immune responses of plants, insects and mammals. We developed an Arabidopsis thaliana leaf cell system based on the induction of early-defence gene transcription by flagellin, a highly conserved component of bacterial flagella that functions as a PAMP in plants and mammals. Here we identify a complete plant MAP kinase cascade (MEKK1, MKK4/MKK5 and MPK3/MPK6) and WRKY22/WRKY29 transcription factors that function downstream of the flagellin receptor FLS2, a leucine-rich-repeat (LRR) receptor kinase. Activation of this MAPK cascade confers resistance to both bacterial and fungal pathogens, suggesting that signalling events initiated by diverse pathogens converge into a conserved MAPK cascade.

Arabidopsis↗