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Results for “Immunity, Innate”

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At least 505 records · Page 28Linked to original sources
PubMed2005

Sindbis virus induces transport processes and alters expression of innate immunity pathway genes in the midgut of the disease vector, Aedes aegypti.

The midgut of hematophagous insects is the initial site of infection by arthropod-borne viruses (arboviruses) and plays a crucial role in vector competence. To further understand processes that occur in the midgut in response to infection by an arbovirus, DNA microarrays were used to analyze gene expression changes following infection by the alphavirus, Sindbis (MRE16 Malaysian strain). Midgut transcription profiles from mosquitoes fed blood containing 10(8)pfu/ml of virus were compared with those from mosquitoes ingesting blood meals having no virus. Transcription profiles from both experimental groups were analyzed at 1, 4, and 8 days post-feeding. Among the many transcription changes observed by microarray analysis, the most dramatic involved three genes that had 25-40-fold increases in transcript levels in virus infected mosquitoes at 4 days post-infection. These genes were synaptic vesicle protein-2 (SV2), potassium-dependent sodium/calcium exchanger (NCKX), and a homologue of Caenorhabditis elegans Unc-93, a putative component of a two-pore potassium channel. We speculate that these changes represent changes in vesicle transport processes. In addition to these observations, transcript changes were observed in infected mosquitoes that suggested involvement of Toll and c-jun amino terminal kinase immune cascades as a response to viral infection.

Aedes↗
PubMed2004

Natural killer cells and innate immunity to protozoan pathogens.

Natural killer (NK) cells are lymphoid cells that mediate significant cytotoxic activity and produce high levels of pro-inflammatory cytokines in response to infection. During viral infection, NK cell cytotoxicity and cytokine production is induced principally by monocyte-macrophage- and dendritic cell-derived cytokines but virally encoded ligands for NK cells are also beginning to be described. NK derived interferon-gamma (IFN-gamma) production is also essential for control of several protozoal infections including toxoplasmosis, trypanosomiasis, leishmaniasis and malaria. The activation of NK cells by protozoan pathogens is also believed to be cytokine-mediated although some recent studies suggest that direct recognition of parasites by NK cells also occurs. Both indirect signalling via accessory cell-derived cytokines and direct signalling, presumably through NK receptors, are needed in order for human malaria parasites (Plasmodium falciparum) to optimally stimulate NK activity.

Humans↗
PubMed2004

The role of scavenger receptors in pathogen recognition and innate immunity.

Scavenger receptors represent a large family of structurally unrelated distinct gene products, expressed by myeloid and selected endothelial cells and able to recognise modified low-density lipoproteins. They also bind and internalise a variety of microbial pathogens, as well as modified or endogenous molecules derived from the host, and contribute to a range of physiological or pathological processes.

Animals↗
PubMed2006

Innate immune activation and CD4+ T cell priming during respiratory fungal infection.

Aspergillus fumigatus is a mold that causes a spectrum of diseases, including lethal lung infections in immunocompromised humans and allergic asthma in atopic individuals. T helper 1 (Th1) CD4(+) T cells protect against invasive A. fumigatus infections whereas Th2 CD4(+) T cells exacerbate asthma upon inhalation of A. fumigatus spores. Herein, we demonstrate that A. fumigatus-specific T cells were rapidly primed in lymph nodes draining the lung and fully differentiated into interferon-gamma (IFN-gamma)-producing Th1 CD4(+) T cells upon arrival in the airways. T-bet induction in A. fumigatus-specific CD4(+) T cells was enhanced by MyD88-mediated signals in draining lymph nodes, but T cell proliferation, trafficking, and Th1 differentiation in the airways were Toll-like receptor (TLR) and MyD88 independent. Our studies demonstrate that CD4(+) T cell differentiation during respiratory fungal infection occurs incrementally, with TLR-mediated signals in the lymph node enhancing the potential for IFN-gamma production whereas MyD88-independent signals promote Th1 differentiation in the lung.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Imbalance of NKG2D and its inhibitory counterparts: how does tumor escape from innate immunity?

NK cells form a first line of defence against pathogens or host cells that are stressed or cancerous. NK cells express surface receptors that receive signals from the environment and determine their response to foreign or malignant cells. The effector functions of NK cells are regulated by integrated signals across the array of stimulatory and inhibitory receptors engaged upon interaction with target cell surface ligands. NKG2D is a peculiar activating receptor that is expressed as a disulphide-linked homodimer by all NK cells, alphabeta CD8(+) T cells, gammadeltaT cells and murine macrophages. It not only activates NK cells but also delivers co-stimulatory signals to CD8(+) T cells and gammadeltaT cells. The ligands of NKG2D are induced by cellular stress and are specifically expressed by some tumor cells. Recent studies reveal that the expression of MIC and ULBP on human tumor cells is sufficient to overcome the inhibitory effects of MHC class I expression on NK cell killing and indicate that NKG2D provides first line surveillance against stressed or abnormal cells that have been induced to express one of its ligands. However, malignant tumors develop means to control the expression of activating versus inhibitory receptors on immune cells and their ligands on tumor cell themselves in favor of tolerance. Modulating the balance between activating and inhibitory signals through NK cell receptors on NK cells may open a new approach to NK cell-based biotherapy for cancer and infectious diseases.

Animals↗
PubMed2004

NK cells: innate immunity against hematological malignancies?

Recent advances in the treatment of malignant haemopathies enable increased remission and cure rates, however, many patients relapse and finally die. Although specific immunity mediated by cytolytic T-lymphocytes might have an anti-cancer role, tumours escape from T-cell-based immune surveillance using various mechanisms, such as downregulation, mutation or loss of HLA class I molecules. As a consequence, these transformed cells could become targets for natural killer (NK) cells, whose cytotoxic capabilities are not blocked by HLA class I molecule engagement by specific inhibitory receptors. Novel developments in NK-cell research, particularly the identification of the role of non-HLA-restricted activating receptors (and in some cases of their ligands), have recently enabled us to reconsider NK-cell interactions with haematological malignant cells.

Cytotoxicity, Immunologic↗
PubMed2004

Interactions between the innate immune and blood coagulation systems.

Blood coagulation and inflammation are universal responses to infection and there is crosstalk between inflammation and coagulation that can either amplify or dampen the responses. Loss of appropriate interactions between these systems probably contributes to morbidity and mortality in infectious diseases. For instance, inflammatory cytokines and leukocyte elastase can downregulate natural anticoagulant proteins that help to maintain endothelial-cell integrity, control clotting, inhibit vasoactive peptides and dampen leukocyte infiltration into the vessel wall. This Review will summarize our current understanding of the mechanisms involved in the crosstalk between these two important systems.

Blood Coagulation↗
PubMed2006

S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity.

BACKGROUND: The calcium-binding protein S100A12 might provoke inflammation and monocyte recruitment through the receptor for advanced glycation end products. OBJECTIVE: Because inflammation elicited by S100A12 in vivo had characteristics of mast cell (MC) activation, we aimed to define the mechanism. METHODS: Various MC populations were used to test S100A12 activation assessed on the basis of morphology, histamine release, leukotriene production, and cytokine induction. MC dependence of S100A12-provoked inflammation was tested in mice and on the rat microcirculation by means of intravital microscopy. Immunohistochemistry localized S100A12 in the asthmatic lung, and levels in sputum from asthmatic patients were quantitated by means of ELISA. Expression of the receptor for advanced glycation end products was evaluated by means of RT-PCR and Western blotting. RESULTS: S100A12 provoked degranulation of mucosal and tissue MCs in vitro and in vivo and amplified IgE-mediated responses. It induced a cytokine profile indicating a role in innate/T(H)1-mediated responses. S100A12-induced edema and leukocyte rolling, adhesion, and transmigration in the microcirculation were MC dependent. Eosinophils in airway tissue from asthmatic patients were S100A12 positive, and levels were increased in sputum. S100A12 responses were partially blocked by an antagonist to the receptor for advanced glycation end products, but MCs did not express mRNA or protein, suggesting an alternate receptor. CONCLUSION: This novel pathway highlights the potential importance of S100A12 in allergic responses and in infectious and chronic inflammatory diseases. CLINICAL IMPLICATIONS: MC activation by S100A12 might exacerbate allergic inflammation and asthma. S100A12 might provide a novel marker for eosinophilic asthma.

Adult↗
PubMed2004

Innate immune recognition of microbes through Nod1 and Nod2: implications for disease.

Nod1 and Nod2 are cytosolic proteins involved in intracellular recognition of microbes and their products. Recently, it was shown that these proteins recognize different moieties of bacterial peptidoglycan (PGN) mediating non-specific pathogen resistance and possibly generating signals for the adaptive immune response. Moreover, mutations in the gene encoding Nod2 are associated with increased susceptibility to chronic inflammatory disorders.

Adaptor Proteins, Signal Transducing↗
PubMed2005

The role of urokinase in innate immunity against Staphylococcus aureus.

Urokinase (uPA) is a serine protease that not only displays fibrinolytic function but also promotes host leukocytes to home to inflammatory sites. We have recently demonstrated that staphylokinase (SAK), which is a fibrinolytic protein secreted by Staphylococcus aureus, forms complexes with human neutrophil peptides (HNPs), which are members of the defensin family and have anti-microbial properties, thereby inhibiting the bactericidal effects of the HNPs. The aim of this study was to assess whether endogenous uPA, which has fibrinolytic properties similar to those of SAK, binds to HNPs and interferes with SAK/HNPs interaction. To this end, an ELISA was used to analyze the interactions between uPA and HNPs. HMW uPA had the ability to bind to both HNP types. The biological consequences of the formation of this complex were analyzed with respect to its bactericidal properties. HMW uPA killed S. aureus, albeit at relatively high doses (50-100 mug/ml). In contrast, the binding of HMW uPA to HNPs had no impact on the bactericidal functions of the HNPs. Importantly, the addition of HMW uPA to SAK eliminated the ability of SAK to neutralize HNPs. Our results demonstrate that endogenous HMW uPA inhibits S. aureus growth both directly, by cytolysis, and indirectly, by abrogation of the neutralizing effect of SAK on the bactericidal activities of HNPs. These findings indicate novel functions of HMW uPA in the host defense against staphylococcal infections.

Humans↗
PubMed2006

The role of lipopolysaccharide-binding protein in modulating the innate immune response.

Lipopolysaccharide-binding protein (LBP) has a well-established role in Gram-negative infection. New data suggest a more expanded role for LBP as a general recognition molecule. Several bacterial surface components from Gram-positive pathogens are also recognized by this molecule. LBP may also serve as a clinical marker in severe infections and may carry therapeutic potential.

Acute-Phase Proteins↗
PubMed2006

Innate immunity in plants: a continuum of layered defenses.

Plant responses to pathogenic invaders result from recognition of nonself elicitors. Host surveillance proteins activate distinct signaling pathways that induce partially overlapping defensive responses. Pathogen virulence is promoted by inhibition of these pathways. This evolutionary struggle has produced plant immune systems that rely on a continuum of layered defenses.

Bacteria↗
PubMed2005

Mosquito innate immunity: involvement of beta 1,3-glucan recognition protein in melanotic encapsulation immune responses in Armigeres subalbatus.

Beta 1,3-glucan recognition proteins (GRP) have specific affinity for beta 1,3-glucan, a component on the surface of fungi and bacteria. By interacting with beta 1,3-glucan, GRP initiates activation of prophenoloxidase, a key enzyme in the signaling pathway leading to melanotic encapsulation in invertebrates. In this study, we characterize a novel hemocyte-specific GRP from the mosquito, Armigeres subalbatus (AsGRP). The 1.57 kb cDNA clone encodes a 499 deduced amino acid sequence, which contains a region that displays significant similarity to the glucanase-like regions of other GRPs and Gram-negative bacteria binding proteins found in other organisms. AsGRP is constitutively expressed in the hemolymph of adult female mosquitoes, and is upregulated following challenge with Escherichia coli, Micrococcus luteus, and the filarial worm Dirofilaria immitis. AsGRP specifically recognizes curdlan (insoluble beta 1,3-glucan), but not mannose or N-acetyl-D-glucosamine. AsGRP binds a low percentage of E. coli, most M. luteus and D. immitis microfilariae. AsGRP double-stranded RNA interference strongly inhibits melanotic encapsulation of D. immitis in Ar. subalbatus. These results suggest that AsGRP has the capacity to bind to a variety of pathogens, functions as a pattern recognition receptor, and is required for effective melanotic encapsulation immune responses in Ar. subalbatus.

Acetylglucosamine↗