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Results for “pathogen effectors”

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PubMed2006

GLI3-dependent transcriptional repression of Gli1, Gli2 and kidney patterning genes disrupts renal morphogenesis.

Truncating mutations in Gli3, an intracellular effector in the SHH-SMO-GLI signaling pathway, cause renal aplasia/dysplasia in humans and mice. Yet, the pathogenic mechanisms are undefined. Here, we report the effect of decreased SHH-SMO signaling on renal morphogenesis, the expression of SHH target genes and GLI binding to Shh target genes. Shh deficiency or cyclopamine-mediated SMO inhibition disrupted renal organogenesis, decreased expression of GLI1 and GLI2 proteins, but increased expression of GLI3 repressor relative to GLI3 activator. Shh deficiency decreased expression of kidney patterning genes (Pax2 and Sall1) and cell cycle regulators (cyclin D1 and MYCN). Elimination of Gli3 in Shh(-/-) mice rescued kidney malformation and restored expression of Pax2, Sall1, cyclin D1, MYCN, Gli1 and Gli2. To define mechanisms by which SHH-SMO signaling controls gene expression, we determined the binding of GLI proteins to 5' flanking regions containing GLI consensus binding sequences in Shh target genes using chromatin immunoprecipitation. In normal embryonic kidney tissue, GLI1 and/or GLI2 were bound to each target gene. By contrast, treatment of embryonic kidney explants with cyclopamine decreased GLI1 and/or GLI2 binding, and induced binding of GLI3. However, cyclopamine failed to decrease Gli1 and Gli2 expression and branching morphogenesis in Gli3-deficient embryonic kidney tissue. Together, these results demonstrate that SHH-SMO signaling controls renal morphogenesis via transcriptional control of Gli, renal patterning and cell cycle regulator genes in a manner that is opposed by GLI3.

Animals↗

PubMed2004

Analysis of microglial gene expression: identifying targets for CNS neurodegenerative and autoimmune disease.

Microglia are the tissue macrophage of the central nervous system (CNS) and their activation is among the earliest signs of CNS dysfunction and disease. Because microglia express many macrophage markers, they are presumed to act primarily as effectors of CNS inflammation and destruction. While such responses are beneficial to the extent that they destroy CNS pathogens, these responses do have the potential to have neurotoxic outcomes. Consequently, therapies for many CNS neurodegenerative and inflammatory diseases have been directed at suppressing microglial function. There is evidence to suggest that microglia play an important role during CNS development and maintenance of CNS function that may go beyond simple defense against pathogens. Molecular analysis of microglial phenotypes and function has revealed three striking findings: (i) that microglia are a unique CNS-specific type of tissue macrophage; (ii) that they are highly heterogeneous within the healthy CNS; and (iii) that microglial responses are exquisitely tailored to specific regions of the CNS and specific pathological insults. We suggest that ubiquitous suppression (rather than targeted manipulation) of microglial function may fail to fully ameliorate CNS pathology and may even ultimately promote maladaptive outcomes.

Animals↗

PubMed2006

Lipopolysaccharide-induced IL-1 beta production by human uterine macrophages up-regulates uterine epithelial cell expression of human beta-defensin 2.

The uterine endometrium coordinates a wide spectrum of physiologic and immunologic functions, including endometrial receptivity and implantation as well as defense against sexually transmitted pathogens. Macrophages and epithelial cells cooperatively mediate innate host defense against bacterial invasion through the generation of immunologic effectors, including cytokines and antimicrobial peptides. In this study, we demonstrate that stimulation of peripheral blood monocytes and uterine macrophages with bacterial LPS induces the production of biologically active proinflammatory IL-1beta. High doses of estradiol enhance LPS-induced IL-1beta expression in an estrogen receptor-dependent manner. Furthermore, both peripheral blood monocyte- and uterine macrophage-derived IL-1beta induce secretion of antimicrobial human beta-defensin 2 by uterine epithelial cells. These data indicate dynamic immunologic interaction between uterine macrophages and epithelial cells and implicate a role for estradiol in the modulation of the immune response.

Adjuvants, Immunologic↗

PubMed1998

The pathophysiology of paraneoplastic neurological syndromes.

Paraneoplastic neurological diseases are a group of neurological disorders associated with neoplastic tumors but not due to tumoral extension, metabolic, infectious, vascular or toxic complications of these tumors or their treatment. In the majority of paraneoplastic neurological disorders, circulating autoantibodies directed against neurons have been found in the serum and/or the CSF suggesting, and in some cases implicating, autoimmunity in the pathophysiology of these diseases. The finding of autoimmune phenomena during the course of paraneoplastic neurological disorders is of importance: from a practical point of view, since the detection of anti-neuronal autoantibodies is of great diagnostic help and should lead to the thorough search of the associated tumor often at an early stage of its development; from a theoretical point of view, these disorders represent a peculiar type of molecular mimicry. Tumoral neontigens having structural homology or identity with neuronal autoantigens elicit autoreactivity. The immunological effector mechanisms involved in the pathophysiology of paraneoplastic syndromes appear to differ according to the disease: autoantibodies are pathogenic in Lambert-Eaton syndrome whereas, in paraneoplastic cerebellar degeneration and in the Hu syndrome, the cellular immune response might play a greater role.

Encephalomyelitis↗

PubMed1999

[Bacterial infection and production of immunoglobulin in the tonsil].

Immunoglobulin (Ig) isotype switching is the process whereby B cells initially expressing IgM and/or IgD on their surface switch to other Ig heavy-chain loci. We demonstrated that TGF-beta, IL-10 and VIP in the presence of CD40 mAb, can induce isotype switching for IgA in human tonsillar B cells by the generation of switch circular DNA (S alpha/S mu), the induction of alpha germ-line transcripts and a significant amount of IgA production. IgA is the predominant immunoglobulin effector molecule of mucosal immunity that functions as the first line of specific immunologic defense against many microbial pathogens. However, IgA causes IgA nephropathy. We investigated here, whether tonsillar mononuclear cells from patients with IgA nephropathy produce HP-specific IgA and/or IgA-related cytokines by stimulation with components of HP outer membranes (OMHP). HP-specific IgA was predominately induced by tonsillar mononuclear cells of IgA nephropathy, compared to those from chronic tonsillitis. Production of IL-10 and TGF-beta was enhanced by stimulation with OMHP in tonsillar mononuclear cells from IgA nephropathy. These results suggested that local infection of HP and HP-specific IgA induction in the tonsil are associated with pathogens in IgA nephropathy.

Bacterial Infections↗

PubMed1988

Differentiation of murine macrophages to express nonspecific cytotoxicity for tumor cells results in L-arginine-dependent inhibition of mitochondrial iron-sulfur enzymes in the macrophage effector cells.

Previous studies show that cytotoxic activated macrophages cause a reproducible pattern of metabolic inhibition in viable tumor target cells. This includes inhibition of DNA synthesis, two oxidoreductases of the mitochondrial electron transport chain (NADH: ubiquinone oxidoreductase and succinate: ubiquinone oxidoreductase), and the citric acid cycle enzyme aconitase. This pattern of metabolic inhibition is induced by a cytotoxic activated macrophage associated biochemical pathway with L-arginine deimination activity that synthesizes L-citrulline from L-arginine and oxygenated nitrogen derivatives from the imino nitrogen removed from the guanido group of L-arginine. Here we report that macrophages activated in vivo by infection with bacillus Calmette-Guérin or in vitro by murine rIFN-gamma or murine IFN-alpha/beta (in the presence of the second signal LPS in all cases) develop inhibition of aconitase and the same two oxidoreductases of the mitochondrial electron transport chain as was documented earlier in target cells of cytotoxic activated macrophages. In addition, this pattern of metabolic inhibition which develops in cytotoxic activated macrophages is caused by the L-arginine-dependent effector mechanism. Inhibition of mitochondrial respiration by effectors of the L-arginine-dependent cytotoxicity system results in a compensatory increase in activity of the glycolytic pathway. We speculate that the pattern of metabolic inhibition induced in cytotoxic activated macrophages by the L-arginine-dependent effector system causes changes in the macrophage intracellular environment that increases resistance to certain facultative and obligate intracellular pathogens.

Aconitate Hydratase↗

PubMed1994

Recombinant L7/L12 ribosomal protein and gamma-irradiated Brucella abortus induce a T-helper 1 subset response from murine CD4+ T cells.

Immunity to Brucella abortus crucially depends on antigen (Ag)-specific T-cell mediated activation of macrophages, which are the major effectors of cell-mediated killing of this organism. Ribosomal preparations have been used as vaccines against several pathogens, including B. abortus, conferring a high degree of protection. In the present study, we have examined the pattern of T-helper (Th) cell response from infected BALB/c mice after in vitro stimulation with recombinant (r) L7/L12 ribosomal protein or gamma-irradiated B. abortus. In addition to Ag-specific proliferation, CD4+ T cells were tested for interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma) mRNA expression and secretion. Detection of cytokine transcripts and secreted cytokines was performed using reverse transcriptase (RT)-polymerase chain reaction (PCR) and specific ELISA assays. Primed CD4+ T cells proliferated to the recombinant protein or whole B. abortus. The functional cytokine profile of the proliferating cells was typical of a Th1 cell phenotype, as we detected transcripts for IL-2 and IFN-gamma but not IL-4. Among the cytokines analysed, only IFN-gamma produced in the Th cell culture supernatants was detected by ELISA when bacteria or recombinant protein were used. Thus, rL7/L12 ribosomal protein and gamma-irradiated B. abortus preferentially stimulated IFN-gamma-producing Th1 cells after in vitro stimulation. The results of this study provide for the first time an explanation of why ribosomal vaccines may protect against intracellular infections, and an experimental basis for identifying polypeptides from a pathogen which stimulates the desired cytokine profile and Th cell response crucial for the design of genetically engineered candidate vaccines.

Animals↗

PubMed2003

Crosstalk between LXR and toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism.

The liver X receptors (LXR) alpha and beta are regulators of cholesterol metabolism and determinants of atherosclerosis susceptibility. Viral and bacterial pathogens have long been suspected to be modulators of atherogenesis; however, mechanisms linking innate immunity to cholesterol metabolism are poorly defined. We demonstrate here that pathogens interfere with macrophage cholesterol metabolism through inhibition of the LXR signaling pathway. Activation of Toll-like receptors (TLR) 3 and 4 by microbial ligands blocks the induction of LXR target genes including ABCA1 in cultured macrophages as well as in aortic tissue in vivo. As a consequence of these transcriptional effects, TLR3/4 ligands strongly inhibit cholesterol efflux from macrophages. Crosstalk between LXR and TLR signaling is mediated by IRF3, a specific effector of TLR3/4 that inhibits the transcriptional activity of LXR on its target promoters. These findings highlight a common mechanism whereby bacterial and viral pathogens may modulate macrophage cholesterol metabolism and cardiovascular disease.

ATP Binding Cassette Transporter 1↗

PubMed2001

Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens.

Eosinophils remain among the most enigmatic of cells, as our appreciation of their detrimental activities--e.g., asthma and allergic disease--far outweighs our understanding of their beneficial effects. Among the major secretory effector proteins of eosinophils are the ribonucleases eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in primates and their orthologs, the eosinophil-associated ribonucleases (EARs) in rodents. The rapid diversification observed among these ribonucleases suggested that the ultimate target(s) might be similarly efficient at generating sequence diversity while maintaining an unalterable susceptibility to ribonucleolytic cleavage. This has prompted us to consider a role for these proteins and by extension, for eosinophils, in host defense against single-stranded RNA virus pathogens. We detail our studies of the antiviral activity of eosinophils and eosinophil ribonucleases against respiratory syncytial virus (RSV) in vitro and the related, natural rodent pathogen, pneumonia virus of mice (PVM), in vivo, and consider the possibility that antiviral host defense and the dysregulated responses leading to asthma represent opposing sides of an eosinophil-mediated double-edged sword.

Animals↗

PubMed2001

Dietary conjugated linoleic acid modulates phenotype and effector functions of porcine CD8(+) lymphocytes.

In vivo vaccination and challenge studies have demonstrated that CD8(+) lymphocytes are essential for the development of cell-mediated protection against intracellular pathogens and neoplastic cells. Depletion of peripheral blood CD8(+) cells interferes with clearance of viruses and intracellular fungi, induction of delayed type hypersensitivity responses and antitumoral activity. In contrast to humans or mice, porcine peripheral CD8(+) lymphocytes are characterized by a heterogeneous expression pattern (i.e., CD8alphabeta and CD8alphaalpha) that facilitates the study of distinctive traits among minor CD8(+) cell subsets. A factorial (2 x 2) arrangement within a split-plot design, with 16 blocks of two littermate pigs as the experimental units for immunization treatment (i.e., unvaccinated or vaccinated with a proteinase-digested Brachyspira hyodysenteriae bacterin) and pig within block as the experimental unit for dietary treatment (soybean oil or conjugated linoleic acid) were used to investigate the phenotypic and functional regulation of CD8(+) cells by dietary conjugated linoleic acid (CLA). Dietary CLA supplementation induced in vivo expansion of porcine CD8(+) cells involving T-cell receptor (TCR)gammadeltaCD8alphaalpha T lymphocytes, CD3(-)CD16(+)CD8alphaalpha (a porcine natural killer cell subset), TCRalphabetaCD8alphabeta T lymphocytes and enhanced specific CD8(+)-mediated effector functions (e.g., granzyme activity). Expansion of peripheral blood TCRalphabetaCD8alphabeta cells was positively correlated (r = 0.89, P < 0.01) with increased percentages of CD8alphabeta(+) thymocytes. Functionally, CLA enhanced the cytotoxic potential of peripheral blood lymphocytes and proliferation of TCRgammadeltaCD8alphaalpha cells. Collectively, these results indicate that dietary CLA enhances cellular immunity by modulating phenotype and effector functions of CD8(+) cells involved in both adaptive and innate immunity.

Animals↗

PubMed2026

Spatial niche remodeling of senescent liver-resident immune cells and its role in chronic liver diseases.

The liver serves the triple functions of metabolism, detoxification, and immune surveillance. Its unique immune microenvironment is shaped by continuous exposure to gut-derived antigens, pathogen-associated molecular patterns (PAMPs), and metabolites arriving via the portal vein, necessitating a delicate equilibrium between immune tolerance and effector activation. This equilibrium relies on the coordinated activities of diverse liver-resident immune cell populations-including Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), dendritic cells (DCs), tissue-resident memory T cells (TRM), innate-like T cells, including mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, and γδ T cells, innate lymphoid cells (ILCs, encompassing conventional NK cells and helper ILC subsets), and neutrophils. With advancing age and chronic injury, these resident immune cell populations undergo profound senescence-associated phenotypic reprogramming that is spatially organized along the portal-to-central axis of the hepatic lobule. Key mechanisms include: telomere dysfunction and DNA damage accumulation driving persistent activation of p53/p21 and p16/Rb pathways; mitochondrial dysfunction with mitochondrial DNA (mtDNA) leakage fueling the senescence-associated secretory phenotype (SASP) via the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway; epigenetic age acceleration, including genome-wide H3K27me3 heterochromatinization; and metabolic reprogramming toward glycolysis and lipid accumulation. This review proposes a "spatial niche remodeling" framework to integrate these cell-intrinsic senescence programs with their lobular context, intercellular communication network rewiring, and pathogenic roles across the spectrum of chronic liver disease-from steatosis through steatohepatitis, fibrosis, cirrhosis, to hepatocellular carcinoma. We critically evaluate emerging senotherapeutic strategies targeting specific liver-resident immune cell subsets, discuss the barriers to clinical translation, and identify priority areas for future investigation, including the application of spatial multi-omics, humanized models, and epigenetic clock-guided clinical trials.

Kupffer cells↗

PubMed2006

Recognition and elimination of diversified pathogens in insect defense systems.

The elimination of infectious non-self by the host defense systems of multicellular organisms requires a variety of recognition and effector molecules. The diversity is generated in somatic cells or encoded in the germ-line. In adaptive immunity in jawed vertebrates, the diversity of immunoglobulins and antigen receptors is generated by gene rearrangements in somatic cells. In innate immunity, various effector molecules and pattern recognition receptors, such as antimicrobial peptides and peptidoglycan recognition proteins, are encoded in the germ-line of multicellular organisms, including insects and jawed vertebrates. In the present review, we discuss how insect host defense systems recognize and eliminate a multitude of microbes via germ-line-encoded molecules, including recent findings that a Drosophila member of the immunoglobulin superfamily is extensively diversified by alternative splicing in somatic immune cells and participates in the elimination of bacteria.

Alternative Splicing↗

PubMed2003

Pathogenicity of Toxoplasma gondii through B-2 cell-mediated downregulation of host defense responses.

IFN-gamma is the primary mediator of anti-parasite effector mechanisms against Toxoplasma gondii. After intraperitoneal infection with the Fukaya strain of T. gondii, unirradiated IFN-gamma knock-out (GKO) mice transferred with wild type (WT) CD8+ effector T cells from infected mice failed to induce the production of IFN-gamma and died, whereas irradiated (IR) GKO mice transferred with WT CD8+ T cells induced IFN-y production and survived more than 6 months. IR GKO mice transferred with WT CD8+ T cells together with GKO B-2 cells died 8 days after infection, whereas those transferred with WT CD8+ T cells together with B-la or T cells survived. B-2 cells of infected GKO mice activated CD11b+ cells for IL-4 production, and down-regulated NO release, STAT1 phosphorylation, and interferon regulatory factor-1 expression in the peritoneal exudates cells of IR GKO mice transferred with WT CD8+ T cells together with GKO B-2 cells after infection. Thus, B-2 cells in T. gondii-infected mice act as suppressor cells in the host defense of infected mice.

Adoptive Transfer↗

PubMed1999

Granzymes are the essential downstream effector molecules for the control of primary virus infections by cytolytic leukocytes.

Analysis of perforin-deficient mice has identified the cytolytic pathway and perforin as the preeminent effector molecule in T cell-mediated control of virus infections. In this paper, we show that mice lacking both granzyme A (gzmA) and granzyme B (gzmB), which are, beside perforin, key constituents of cytolytic vesicles, are as incapable as are perforin-deficient mice of controlling primary infections by the natural mouse pathogen ectromelia, a poxvirus. Death of gzmAxgzmB double knockout mice occurred in a dose-dependent manner, despite the expression of functionally active perforin and the absence of an intrinsic defect to generate splenic cytolytic T cells. These results establish that both gzmA and gzmB are indispensable effector molecules acting in concert with perforin in granule exocytosis-mediated host defense against natural viral pathogens.

Animals↗

PubMed2002

Regulation of mRNA expression in macrophages after Yersinia enterocolitica infection. Role of different Yop effectors.

The Yop virulon, which comprises a complete type III secretion system and secreted proteins, allows bacteria from the genus Yersinia to resist the nonspecific immune response of the host. This virulon, which is encoded by a plasmid called pYV in Yersinia enterocolitica, enables extracellular bacteria to inject six Yop effectors (YopE, -H, -T, -O, -P, -M) into the host cell. To investigate the role of YopP, YopM, and the other pYV-encoded factors on the expression of the host cell genes, we characterized the transcriptome alterations in infected mouse macrophages using the microarray technique. PU5-1.8 macrophages were infected either with an avirulent (pYV(-)), a wild type (pYV(+)), or two knockout (yopP(-) and yopM(-)) mutants of Y. enterocolitica. Expression alterations in response to Y. enterocolitica infection were monitored for 6657 genes. Among those, 857 genes were affected, 339 of which were specifically regulated by the action of the Yop virulon. Further analysis of those 339 genes allowed identification of specific targets of YopP, YopM, or the other pYV-encoded factors. According to these results, the main action of the Yop virulon is to counteract the host cell pro-inflammatory response to the infection. YopP participates to this inhibition, whereas another pYV-encoded factor appears to also be involved in this down-regulation. Besides, YopM was found to induce the regulation of genes involved in cell cycle and cell growth, revealing for the first time an in vitro effect for YopM. In addition to YopM, other pYV factors distinct from YopP affected the expression of genes involved in cycling. In conclusion, these results provide new insight into the mechanisms of Yersinia pathogenicity by identifying the changes in host genes expression after infection and highlight the concerted actions of the different Yop effectors.

Adhesins, Bacterial↗

PubMed2006

Genome-wide transcriptional analysis of the Arabidopsis thaliana interaction with the plant pathogen Pseudomonas syringae pv. tomato DC3000 and the human pathogen Escherichia coli O157:H7.

Pseudomonas syringae pv. tomato DC3000 (Pst) is a virulent pathogen that causes disease on tomato and Arabidopsis. The type III secretion system (TTSS) plays a key role in pathogenesis by translocating virulence effectors from the bacteria into the plant host cell, while the phytotoxin coronatine (COR) contributes to virulence and disease symptom development. Recent studies suggest that both the TTSS and COR are involved in the suppression of host basal defenses. However, little is known about the interplay between the host gene expression changes associated with basal defenses and the virulence activities of the TTSS and COR during infection. In this study, we used the Affymetrix full genome chip to determine the Arabidopsis transcriptome associated with basal defense to Pst DC3000 hrp mutants and the human pathogenic bacterium Escherichia coli O157:H7. We then used Pst DC3000 virulence mutants to characterize Arabidopsis transcriptional responses to the action of hrp-regulated virulence factors (e.g. TTSS and COR) during bacterial infection. Additionally, we used bacterial fliC mutants to assess the role of the pathogen-associated molecular pattern flagellin in induction of basal defense-associated transcriptional responses. In total, our global gene expression analysis identified 2800 Arabidopsis genes that are reproducibly regulated in response to bacterial pathogen inoculation. Regulation of these genes provides a molecular signature for Arabidopsis basal defense to plant and human pathogenic bacteria, and illustrates both common and distinct global virulence effects of the TTSS, COR, and possibly other hrp-regulated virulence factors during Pst DC3000 infection.

Abscisic Acid↗

PubMed1999

Response of murine and normal human skin to injection of allogeneic blood-derived psoriatic immunocytes: detection of T cells expressing receptors typically present on natural killer cells, including CD94, CD158, and CD161.

BACKGROUND: The genetic and immunological basis for psoriasis is unknown. Through the use of a severe combined immunodeficient mouse-human skin model, T cells have been shown to induce psoriasis, which points to a pathological role for such immunocompetent cells. During ongoing studies using this model, a previously overlooked subset of immunocytes expressing receptors typically present on natural killer (NK) cells was discovered, which may shed new light on the genetic susceptibility for psoriasis. OBSERVATIONS: Immunocytes from a psoriatic patient were injected into engrafted allogeneic normal human skin and produced a psoriatic plaque. Moreover, the disturbed epidermal environment spread to induce a greater than 20-fold increase in thickness of adjacent mouse epidermis with prominent elongation of rete pegs. Thus, rather than observing the predicted graft-vs-host reaction in the allogeneic human or xenogeneic mouse skin, injection of psoriatic immunocytes triggered psoriasis. To explore a potential mechanism to explain the lack of cytopathic effect by psoriatic T cells, immunostaining to detect inhibitory receptors normally present on NK cells was performed. These receptors include surface molecules that can inhibit NK cell proliferation, cytokine release, and/or cytotoxicity (ie, killer cell inhibitory receptors [KIRs]), as well as those that may activate NK cell cytotoxicity (ie, killer cell activating receptors [KARs]). The blood-derived psoriatic immunocytes in the skin graft expressed CD94, CD158a, CD158b, NKB1,and CD161. Furthermore, both hyperplastic human and murine keratinocytes express the major histocompatibility complex (MHC) class I-like CD1d protein, which has been shown to be a specific ligand of T cells expressing CD161 and other NK cell-associated receptors. CONCLUSIONS: Since several KIRs and KARs are known to recognize various class I MHC alleles, and because psoriasis inheritance and susceptibility has been linked to various class I MHC molecules, we propose a novel hypothesis in which the pathogenic T cells are postulated to express an assortment of KIRs and KARs. These interactions may produce direct activation without any exogenous antigen, and at the same time block the cytotoxic effector function of these activated immunocytes in this allogeneic and xenogeneic experimental setting. In addition, human T cells expressing CD161 may be capable of interacting with human and murine CDT1d expressed by the epidermal keratinocytes. These unexpected findings demonstrate that psoriasis is an immunological disease in which pathogenic T cells rather than epidermal keratinocytes are of primary importance. Functional studies will determine if targeting this previously overlooked population of immunocytes with blocking reagents will generate a novel immunotherapeutic strategic pathway for psoriasis, and whether disease susceptibility and/or incidence patterns can be explained by genetic abnormalities involving these ligand-receptor interactions.

Animals↗

PubMed1986

Ixodid-host immune interaction. Identification and characterization of relevant antigens and tick-induced host immunosuppression.

Ixodid ticks are the most important vectors of pathogens to domestic and wild animals. It is established that cattle and laboratory animal species acquire resistance to tick infestation; acquired resistance has an immunological basis consisting of cell-mediated, antibody-mediated and complement-dependent effector mechanisms. Even though acquired resistance to tick feeding is expressed, host immune competence is possibly impaired during the course of tick feeding. Ixodid-induced transient immunosuppression could possibly facilitate the transmission of vector-borne pathogens and/or enhance tick feeding capabilities in the presence of a host immune response to the hematophagous arthropod. Tick tissue extracts have been used to artificially induce resistance to ixodid feeding, and this has become an area of increasing interest as a possible strategy for tick control. It is essential to have defined antigenic molecules for analysis of host responses to infestation, characterization of immunopathologic processes and for vaccine development. This report focuses on attempts to identify, characterize and isolate tick immunogens. Protein immunoblotting, utilizing sera from animals of different genetic composition and infestation patterns, was used to detect a number of tick polypeptides which are reactive with sera of infested hosts. It is clear that infestation with one ixodid species stimulates antibodies reactive with molecules derived from the sensitizing species and/or tick species in the same genus or different genera. This approach is used to identify molecules that are good candidates for use in immunization studies and for analysis of mechanisms involved in acquisition and expression of resistance to tick feeding.

Animals↗