SEARCH · PubMed Health

Results for “Innate Immunity Recognition”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

PubMed2006

The CARMA1 signalosome links the signalling machinery of adaptive and innate immunity in lymphocytes.

The recognition of antigen by B- or T-cell receptors initiates an intracellular signalling cascade that results in the nuclear translocation and activation of the transcription factor nuclear factor-kappaB (NF-kappaB). NF-kappaB is an important regulator of lymphocyte development and function, and its dysregulation is associated with many immune disorders. Defining the mechanisms that transmit signals from the antigen receptor to NF-kappaB is therefore an important goal for immunologists. In this Review, we merge information gleaned from research of the innate immune system with what we know about antigen-receptor signals in the adaptive immune system, to propose a cohesive model of how antigen receptors activate NF-kappaB.

Animals↗

PubMedDate not supplied

Role of lipopolysaccharide susceptibility in the innate immune response to Salmonella typhimurium infection: LPS, a primary target for recognition of Gram-negative bacteria.

Lipopolysaccharide is an important recognition marker by virtue of which the innate immune system senses and reacts against Gram-negative bacteria invading the LPS susceptible host. This review deals with the factors affecting LPS susceptibility and with the role of the latter in the course and outcome of Salmonella typhimurium infection.

Animals↗

PubMed2000

Molecular events of bacterial-induced maturation of dendritic cells.

In order to protect the body from infectious microorganisms, mammals have developed powerful lines of defense, consisting in innate and adaptive immune responses. The innate response is phylogenetically more ancient and, for a long time, it has been considered to be broadly directed to microorganisms. However, the discovery of a new class of receptors, involved in recognition of patterns characteristic of groups of microorganisms (the toll-like receptor family) has re-evaluated the role of the innate immune system as a discriminating system. Indeed, there is increasing evidence that the induction of different types of effector adaptive responses are directed by the innate immune system after recognition of particular groups of pathogens. The central role of Dendritic cells (DC) in the induction of adaptive immune responses towards infectious agents has been extensively described, but, recently, a new role of DC as a link between the non-antigen- and the antigen-specific responses has been proposed. DC have, indeed, the capacity to recruit and activate cells of the innate immune system upon inflammation. Thus. understanding the interaction of bacteria with DC, and the early molecular events resulting from this interaction may shed some light on the mechanisms of initiation of the immune response to infectious agents and on aspects of invasiveness, pathogenicity, and the persistence of certain bacteria.

Animals↗

PubMed2005

The involvement of the macrophage mannose receptor in the innate immune response to infection with parasite Trichinella spiralis.

The macrophage mannose receptor (MR) is a pattern recognition receptor of the innate immune system that binds to microbial structures bearing mannose, fucose and N-acetylglucosamine on their surface. The MR can mediate endocytosis and phagocytosis, as well as activation of macrophages and antigen presentation. Since Trichinella spiralis antigens are rich in oligomannose residues, we investigated whether a mannose-recognizing receptor, such as the MR, participated in the host-parasite interaction. The results show that the MR (either on the surface of macrophages or in the purified form) recognizes and binds components of T. spiralis muscle larvae. The presence of parasites provoked activation of peritoneal macrophages, which was indicated by down-regulation of MR expression, and the stimulation of NO secretion. In vitro stimulation of macrophages with T. spiralis components resulted in increased NO and IL-6 production. However, while the MR was partially involved in stimulation of NO production, it did not mediate IL-6 secretion.

Animals↗

PubMed2006

Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer.

Clinical and epidemiologic studies have suggested an association between infectious agents and chronic inflammatory disorders and cancer. Better understanding of microbial pattern-recognition receptors and innate immune signaling pathways of the host is helping to elucidate the connection between microbial infection and chronic disease. We propose that a key aspect of pathogenesis is an aberrant epithelial barrier that can be instigated by microbial toxins, environmental insults, or the genetic predisposition of the host. Loss of epithelial integrity results in activation of resident inflammatory cells by microbial invaders or endogenous ligands. When coupled with a failure of normal control mechanisms that limit leukocyte activation, a cascade is established that induces chronic inflammation and its consequences. Here, we outline this mechanistic framework and briefly review how alteration of innate immune response genes in murine models can provide insights into the potential microbial origins of diverse conditions including Crohn's disease, psoriasis, atherosclerosis, diabetes, and liver cancer.

Animals↗

PubMed2006

N-(3-oxo-acyl)homoserine lactones signal cell activation through a mechanism distinct from the canonical pathogen-associated molecular pattern recognition receptor pathways.

Innate immune system receptors function as sensors of infection and trigger the immune responses through ligand-specific signaling pathways. These ligands are pathogen-associated products, such as components of bacterial walls and viral nuclear acids. A common response to such ligands is the activation of mitogen-activated protein kinase p38, whereas double-stranded viral RNA additionally induces the phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2alpha). Here we have shown that p38 and eIF2alpha phosphorylation represent two biochemical markers of the effects induced by N-(3-oxo-acyl)homoserine lactones, the secreted products of a number of Gram-negative bacteria, including the human opportunistic pathogen Pseudomonas aeruginosa. Furthermore, N-(3-oxo-dodecanoyl)homoserine lactone induced distension of mitochondria and the endoplasmic reticulum as well as c-jun gene transcription. These effects occurred in a wide variety of cell types including alveolar macrophages and bronchial epithelial cells, requiring the structural integrity of the lactone ring motif and its natural stereochemistry. These findings suggest that N-(3-oxo-acyl)homoserine lactones might be recognized by receptors of the innate immune system. However, we provide evidence that N-(3-oxo-dodecanoyl)homoserine lactone-mediated signaling does not require the presence of the canonical innate immune system receptors, Toll-like receptors, or two members of the NLR/Nod/Caterpillar family, Nod1 and Nod2. These data offer a new understanding of the effects of N-(3-oxo-dodecanoyl)homoserine lactone on host cells and its role in persistent airway infections caused by P. aeruginosa.

4-Butyrolactone↗

PubMed2003

Toll-like receptor-9 induced by physical trauma mediates release of cytokines following exposure to CpG motif in mouse skin.

The skin plays a crucial role in defence against microbial infection via the innate immune system, but the exact cellular mechanisms of this defence are not well understood. Toll-like receptors (TLRs), a newly recognized 10-member family of vertebrate pattern recognition receptors (PRRs), have been identified as crucial mediators of innate immune recognition. Although both TLR2 and TLR4 have been detected in normal human skin, little is known about the expression and function of TLR9, a CpG motif receptor, in skin. In this study, reverse transcription-polymerase chain reaction and in situ hybridization analysis were used to identify TLR9 mRNA expression in mouse skin. Results showed that TLR9 mRNA was not detected in normal mouse skin, but its presence in skin could be induced by intradermal injection of either normal saline, or the bacteria-based CpG motif in a time- and volume-dependent manner. Furthermore, intradermal injection of CpG motif induced increased expression of mRNAs for proinflammatory cytokines such as interleukin (IL)-1, IL-6, IL-12 and tumour necrosis factor alpha. This suggests that TLR9, while not present basally in skin, can be induced by physical trauma and then mediate responses to CpG motif. In conclusion, TLR9 is involved in the innate immune response in skin and that it may have a role in secondary inflammation following physical trauma such as epidermal damage or microbial infection. This role of TLR9 may help explain the previously identified enhancement of DNA immunization by CpG ODN.

Animals↗

PubMed2006

Receptor protein kinases--pattern recognition receptors in plant immunity.

Plant innate immunity is activated either upon perception of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) or upon resistance (R) protein-mediated recognition of pathogen race-specific effector molecules. Although many plant R proteins have been identified, there is only limited knowledge about plant PRRs. Recently, Cyril Zipfel et al. identified a second Arabidopsis leucine-rich repeat receptor protein kinase implicated in PAMP perception, which suggests that several members of this large protein family function as pattern recognition receptors.

Arabidopsis↗

PubMed2005

Innate immunity conferred by Toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation.

OBJECTIVE: In gout, incompletely defined molecular factors alter recognition of dormant articular and bursal monosodium urate monohydrate (MSU) crystal deposits, thereby inducing self-limiting bouts of characteristically severe neutrophilic inflammation. To define primary determinants of cellular recognition, uptake, and inflammatory responses to MSU crystals, we conducted a study to test the role of Toll-like receptor 2 (TLR-2), TLR-4, and the cytosolic TLR adapter protein myeloid differentiation factor 88 (MyD88), which are centrally involved in innate immune recognition of microbial pathogens. METHODS: We isolated bone marrow-derived macrophages (BMDMs) in TLR-2-/-, TLR-4-/-, MyD88-/-, and congenic wild-type mice, and assessed phagocytosis and cytokine expression in response to endotoxin-free MSU crystals under serum-free conditions. MSU crystals also were injected into mouse synovium-like subcutaneous air pouches. RESULTS: TLR-2-/-, TLR-4-/-, and MyD88-/- BMDMs demonstrated impaired uptake of MSU crystals in vitro. MSU crystal-induced production of interleukin-1beta (IL-1beta), tumor necrosis factor alpha, keratinocyte-derived cytokine/growth-related oncogene alpha, and transforming growth factor beta1 also were significantly suppressed in TLR-2-/- and TLR-4-/- BMDMs and were blunted in MyD88-/- BMDMs in vitro. Neutrophil influx and local induction of IL-1beta in subcutaneous air pouches were suppressed 6 hours after injection of MSU crystals in TLR-2-/- and TLR-4-/- mice and were attenuated in MyD88-/- mice. CONCLUSION: The murine host requires TLR-2, TLR-4, and MyD88 for macrophage activation and development of full-blown neutrophilic, air pouch inflammation in response to MSU crystals. Our findings implicate innate immune cellular recognition of naked MSU crystals by specific TLRs as a major factor in determining the inflammatory potential of MSU crystal deposits and the course of gouty arthritis.

Adaptor Proteins, Signal Transducing↗

PubMed2004

L-ficolin is a pattern recognition molecule specific for acetyl groups.

L-ficolin and H-ficolin are molecules of the innate immune system. Upon recognition of a suitable target they activate the complement system. The ligand recognition structure of ficolins is contained within a fibrinogen-like domain. We examined the selectivity of the ficolins through inhibiting the binding to bacteria or to beads coupled with N-acetylglucosamine. The binding of L-ficolin to Streptococcus pneumoniae 11F and the beads was inhibited by N-acetylated sugars and not by non-acetylated sugars. However, it was also inhibited by other acetylated compounds. Based on this selectivity L-ficolin is not easily defined as a lectin. The binding of H-ficolin to Aerococcus viridans was not inhibited by any of the sugars or other compounds examined. Based on the selectivity of L-ficolin we developed a new purification procedure involving affinity chromatography on N-acetylcysteine-derivatized Sepharose. The column was loaded in the presence of EDTA and high salt, and L-ficolin was eluted by decreasing the salt concentration. Further purification was achieved by ion exchange chromatography.

Acetylation↗

PubMed2002

Innate immunity in plants and animals: emerging parallels between the recognition of general elicitors and pathogen-associated molecular patterns.

Recent findings have highlighted remarkable similarities in the innate pathogen defense systems of plants, animals and insects. Pathogen-associated molecular patterns (PAMP) that are similar to those activating innate immune responses in animals have been shown to mediate the activation of plant defense. Moreover, recognition complexes that are structurally related to animal PAMP receptors are now being discovered in plants, suggesting a common evolutionary origin of pathogen defense systems in higher eukaryotes.

Animals↗

PubMed2003

[Heat shock proteins as chaperones of the immune response. The optimal stress of life].

The author reviews the complex role of heat-shock proteins during the immune reaction, especially the cellular effects of heat-shock proteins during recognition processes by innate immunity. The pathogenetic role of heat-shock proteins in two multifactorial diseases, inflammatory bowel disease and atherosclerosis, is summarized. A new hypothesis is presented dealing with the "immunodeficiency burden" as the aggregate effect of the genetic polymorphisms resulting in disease susceptibility. According to this mechanism the aggregate effect of polymorphisms resulting in failure of protective immunity determines the susceptibility for the disease in the given subject, when a specific environmental factor is present.

Antigens, CD↗

PubMed2003

Innate recognition of lipopolysaccharide by CD14 and toll-like receptor 4-MD-2: unique roles for MD-2.

Adaptive immunity generally refers to the ability of lymphocytes to recognize microbial, viral and fungal proteins via T cell receptors and antibodies. More ancestral and widespread innate immune mechanisms include those responsible for recognition of microbial glycolipids. Lipopolysaccharide (LPS) is the best studied, and arguably one of the most important of bacterial products because of its role in innate immune responses and endotoxin-mediated sepsis. Converging studies in two independent fields have recently led to the identification of LPS recognition molecules utilized by mammalian cells. Toll-like receptor 4 (TLR4) was identified as a mammalian homologue of the Toll receptor, which recognized fungi in the Drosophila's immune system. Spontaneous and targeted mutations identified TLR4 as an LPS recognition molecule. Separate studies of a Radioprotective 105 (RP105) and MD-1 heterodimer expressed by cells led to the identification of MD-2 as a molecule associated with TLR4. Very recent in vivo studies have now revealed an essential contribution of MD-2 to LPS recognition. These findings further our understanding of protective, as well as detrimental innate immune mechanisms and may lead to new therapies for endotoxin shock.

Animals↗

PubMed2004

Immunological aspects of heat-shock proteins-the optimum stress of life.

This review summarizes the complex role of heat-shock proteins (Hsp) in immune reactions, especially the cellular effects of heat-shock proteins during the recognition processes by innate immunity. The role of heat-shock proteins in the pathogenesis of two multifactorial diseases, i.e. inflammatory bowel disease (IBD) and atherosclerosis is highlighted. A new hypothesis on "immunodeficiency burden" is presented. According to this hypothesis, susceptibility to any multifactorial disease in any given subject and in the presence of specific environmental factors is the aggregate effect of polymorphisms resulting in the failure of protective immunity with consequent disease.

Arteriosclerosis↗

PubMed2006

The role of NK cell recognition of nectin and nectin-like proteins in tumor immunosurveillance.

Natural killer (NK) cells have important functions in the innate immunity to tumors. Recognition of tumor cells by NK cells is mediated by the interaction of activating and inhibitory NK cell receptors with ligands expressed on the tumor target. In addition, NK cell-target cell interactions require the engagement of adhesion molecules that stabilize the cell-cell conjugate. Recently, several novel NK cell receptors have been reported to regulate NK cell adhesion and activation through interaction with ligands of the nectin and nectin-like (Necl) family of adhesion molecules. We here review current knowledge on these receptors, CD226, CD96 and CRTAM, and their role in tumor immunosurveillance.

Animals↗

PubMed1999

Innate immunity in insects: the role of multiple, endogenous serum lectins in the recognition of foreign invaders in the cockroach, Blaberus discoidalis.

Unlike vertebrates, insects do not have an Ab-based nonself recognition system, and must rely totally on innate immunity to defend themselves from microbial invaders. The most likely candidates for recognizing foreign material in insects are the lectins, which have already been shown to be important in mammalian innate immunity. The hemolymph of the cockroach, Blaberus discoidalis, contains multiple lectins, designated BDL1, BDL2, BDL3, and GSL (beta-1,3-glucan-specific lectin), two of which, namely BDL1 and GSL, have close similarities to acute phase reactants. These endogenous molecules, as well as Con A, wheat germ agglutinin, and Helix pomatia agglutinin, have been shown to induce an enhanced phagocytic response by B. discoidalis plasmatocytes. This effect is related to the carbohydrates presented on the surface of the microorganism and to the sugar specificities of the lectins. Thus, the mannose-specific lectins, BDL1 and Con A, both increase the phagocytosis of baker's yeast and Escherichia coli, whereas the N-acetyl-D-glucosamine/N-acetyl-D-galactosamine-specific lectins, BDL2, wheat germ agglutinin, and H. pomatia agglutinin, induce the phagocytosis of Bacillus cereus and E. coli. GSL, specific for beta-1,3-glucan, and the N-acetyl-D-galactosamine-specific BDL3, only enhance the phagocytosis of yeast and B. cereus, respectively. Phenylthiourea, an inhibitor of the prophenoloxidase system, caused either total, partial, or no inhibition of the lectin-induced increase in phagocytosis, indicating that this immune enhancement results, in some cases, from at least two closely linked mechanisms. These results show that the endogenous lectins in the cockroach hemolymph are capable of acting as nonself recognition molecules for a wide range of microorganisms, and thus obviate the necessity of Abs in these animals.

Animals↗

PubMed2005

Human neutrophil gene expression profiling following xenogeneic encounter with porcine aortic endothelial cells: the occult role of neutrophils in xenograft rejection revealed.

The role of innate immune cells in the recognition and activation of xenogeneic endothelium has always been considered secondary to the initial insult of xenoreactive natural antibodies (XNA) and complement. It was argued, however, that innate immune cells are capable of recognizing and activating xenogeneic endothelium in the absence XNA and complement. Here, we show that porcine aortic endothelial cells (PAECs) activate human neutrophils directly. This contact-dependent activation causes a transient calcium rise leading to increased reactive oxygen metabolite (ROM) production. Neutrophil gene-expression profiling using an adenylate uridylate-rich element-based microarray revealed a dramatic change in the neutrophil gene profiles upon exposure to PAECs. The PAEC-dependent neutrophil transcriptional activity was further confirmed by real-time polymerase chain reaction, which revealed a rapid increase in the mRNA message of a number of inflammatory cytokines. The activation of human neutrophils by PAECs was independent of galactose alpha1,3-galactose (Galalpha1,3-gal) structures, as inclusion of saturating concentrations of anti-Galalpha1,3-gal l antibodies had no significant effect. Furthermore, this activation was inhibited in the presence of the calcium chelator 1,2-bis(O-aminophenyl-ethane-ethane)-N,N,N',N'-tetraacetic acid-acetoxymethyl ester and the ROM inhibitor diphelylene iodonium. Our data illustrate the direct activation of innate immune cells by PAECs in the absence of XNA and complement and suggest alternative recognition sites between PAECs and human innate immune cells.

Animals↗

PubMed2003

Collaborative induction of inflammatory responses by dectin-1 and Toll-like receptor 2.

Toll-like receptors (TLRs) mediate recognition of a wide range of microbial products including lipopolysaccharides, lipoproteins, flagellin, and bacterial DNA, and signaling through TLRs leads to the production of inflammatory mediators. In addition to TLRs, many other surface receptors have been proposed to participate in innate immunity and microbial recognition, and signaling through some of these receptors is likely to cooperate with TLR signaling in defining inflammatory responses. In this report we have examined how dectin-1, a lectin family receptor for beta-glucans, collaborates with TLRs in recognizing microbes. Dectin-1, which is expressed at low levels on macrophages and high levels on dendritic cells, contains an immunoreceptor tyrosine-based activation motif-like signaling motif that is tyrosine phosphorylated upon activation. The receptor is recruited to phagosomes containing zymosan particles but not to phagosomes containing immunoglobulin G-opsonized particles. Dectin-1 expression enhances TLR-mediated activation of nuclear factor kappa B by beta-glucan-containing particles, and in macrophages and dendritic cells dectin-1 and TLRs are synergistic in mediating production of cytokines such as interleukin 12 and tumor necrosis factor alpha. Additionally, dectin-1 triggers production of reactive oxygen species, an inflammatory response that is primed by TLR activation. The data demonstrate that collaborative recognition of distinct microbial components by different classes of innate immune receptors is crucial in orchestrating inflammatory responses.

3T3 Cells↗