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At least 235 records · Page 13Linked to original sources

PubMed2006

Natural regulatory T cells and parasites: a common quest for host homeostasis.

This review discusses the roles played by natural CD4+ CD25+ regulatory T cells (natural Tregs) during parasitic infections. Natural Tregs may limit the magnitude of effector responses, which may result in failure to adequately control infection. However, natural Tregs also help to limit collateral tissue damage caused by vigorous antimicrobial immune responses. We discuss the hypothesis that parasites have evolved means to manipulate the host's natural Treg population, thereby generating conditions that secure survival in their vertebrate host for an extended period of time.

Animals↗

PubMed2006

Host propagation permits extreme local adaptation in a social parasite of ants.

The Red Data Book hoverfly species Microdon mutabilis is an extreme specialist that parasitises ant societies. The flies are locally adapted to a single host, Formica lemani, more intimately than was thought possible in host-parasite systems. Microdon egg survival plummeted in F. lemani colonies > 3 km away from the natal nest, from c. 96% to 0% to < 50%, depending on the hoverfly population. This is reflected in the life-time dispersal of females, measured at < 2 m, resulting in oviposition back into the same ant nests for generation after generation. To counter destabilizing effects on the host, Microdon manipulates the social dynamics of F. lemani by feeding selectively on ant eggs and small larvae, which causes surviving larvae to switch development into queens. Infested colonies rear double the number of new queens, thus propagating the vulnerable local genotype and compensating for damage to the host colonies. The consequences of such extreme host specificity for insect conservation are discussed.

Adaptation, Physiological↗

PubMed2006

Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii's ability to alter host behaviour.

With increasing pressure to understand transmissible agents, renewed recognition of infectious causation of both acute and chronic diseases is occurring. Epidemiological and neuropathological studies indicate that some cases of schizophrenia may be associated with environmental factors, such as exposure to the ubiquitous protozoan Toxoplasma gondii. Reasons for this include T. gondii's ability to establish persistent infection within the central nervous system, its ability to manipulate intermediate host behaviour, the occurrence of neurological and psychiatric symptoms in some infected individuals, and an association between infection with increased incidence of schizophrenia. Moreover, several of the medications used to treat schizophrenia and other psychiatric disease have recently been demonstrated in vitro to possess anti-parasitic, and in particular anti-T. gondii, properties. Our aim here was thus to test the hypothesis that the anti-psychotic and mood stabilizing activity of some medications may be achieved, or at least augmented, through their in vivo inhibition of T. gondii replication and invasion in infected individuals. In particular we predicted, using the epidemiologically and clinically applicable rat-T. gondii model system, and following a previously described and neurologically characterized 'feline attraction' protocol that haloperidol (an anti-psychotic used in the treatment of mental illnesses including schizophrenia) and/or valproic acid (a mood stabilizer used in the treatment of mental illnesses including schizophrenia), would be, at least, as effective in preventing the development of T. gondii-associated behavioural and cognitive alterations as the standard anti-T. gondii chemotherapeutics pyrimethamine with Dapsone. We demonstrate that, while T. gondii appears to alter the rats' perception of predation risk turning their innate aversion into a 'suicidal' feline attraction, anti-psychotic drugs prove as efficient as anti-T. gondii drugs in preventing such behavioural alterations. Our results have important implications regarding the aetiology and treatment of such disorders.

Animals↗

PubMed2002

Helicobacter pylori inflammation and immunity.

Gastric inflammation is a significant contributor to the disease process associated with Helicobacter pylori infection. It appears that both bacterial genes and differential host responses make interrelated contributions to gastritis and disease outcome after H. pylori infection. While the cag pathogenicity island (PAI) continues to be a focus for much of this investigation on the bacterial side, other bacterial genes/proteins are certainly important as well. On the host cell side, significant progress is being made defining the eucaryotic signaling cascades induced after host cells interact with H. pylori. The role of host cell cytokines, gastric acid, and mast cells is also being actively studied. Prospects for control of H. pylori associated disease continue to include vaccination. The mechanism(s) for vaccine-mediated control of H. pylori infection and disease remain ill-defined but recent evidence from animal models suggests that the inflammatory response may be involved. Manipulating the host response to H. pylori infection in humans to take advantage of the possible beneficial effects of inflammation, while minimizing its detrimental effects is a significant challenge for the future.

Animals↗

PubMed2006

Pollination niche overlap between a parasitic plant and its host.

Niche theory predicts that species which share resources should evolve strategies to minimise competition for those resources, or the less competitive species would be extirpated. Some plant species are constrained to co-occur, for example parasitic plants and their hosts, and may overlap in their pollination niche if they flower at the same time and attract the same pollinators. Using field observations and experiments between 1996 and 2006, we tested a series of hypotheses regarding pollination niche overlap between a specialist parasitic plant Orobanche elatior (Orobanchaceae) and its host Centaurea scabiosa (Asteraceae). These species flower more or less at the same time, with some year-to-year variation. The host is pollinated by a diverse range of insects, which vary in their effectiveness, whilst the parasite is pollinated by a single species of bumblebee, Bombus pascuorum, which is also an effective pollinator of the host plant. The two species therefore have partially overlapping pollination niches. These niches are not finely subdivided by differential pollen placement, or by diurnal segregation of the niches. We therefore found no evidence of character displacement within the pollination niches of these species, possibly because pollinators are not a limiting resource for these plants. Direct observation of pollinator movements, coupled with experimental manipulations of host plant inflorescence density, showed that Bombus pascuorum only rarely moves between inflorescences of the host and the parasite and therefore the presence of one plant is unlikely to be facilitating pollination in the other. This is the first detailed examination of pollination niche overlap in a plant parasite system and we suggest avenues for future research in relation to pollination and other shared interactions between parasitic plants and their hosts.

Animals↗

PubMed1995

Manipulation of local and systemic host defence in the prevention of perioperative sepsis.

This review addresses some of the immunological issues surrounding the complex problem of perioperative sepsis. It identifies an immunological paradox between the relative immunosuppression of the immediate postoperative period and the relative immune activation of established sepsis, in addition to discussing current knowledge of the mechanisms surrounding these phenomena. Much remains unknown about perioperative immunoregulation; there are a number of potential mechanisms, however, whereby local and systemic immune defences can be modified or enhanced. Provided patients at risk can be identified, such manipulations may find application in preventing infection and sepsis after surgery.

Humans↗

PubMed1991

Chromosomal integration of plasmid DNA by homologous recombination in Enterococcus faecalis and Lactococcus lactis subsp. lactis hosts harboring Tn919.

Integration of pCI192, a pBR322-derived vector plasmid containing homology to the chromosomally located conjugative transposon Tn919 was observed in two strains that harbor Tn919, namely, Enterococcus faecalis GF590 and Lactococcus lactis subsp. lactis CH919. Hybridization analysis indicated that single-copy integration of the plasmid had occurred at low frequency. The Tn919::plasmid structure was conjugated from an E. faecalis donor to a L. lactis recipient, although at lower frequencies than was Tn919. Segregation of the tetracycline and chloramphenicol resistance markers during conjugation was observed. The integration strategy described allows for DNA manipulations to be performed in an easily manipulated model host strain with the subsequent transfer of integrated structures by conjugation to any strain capable of receiving Tn919. The results indicate that homologous recombination events may be used to introduce plasmid-encoded genes to the lactococcal chromosome.

Chromosomes, Bacterial↗

PubMed2003

Purine synthesis and increased Agrobacterium tumefaciens transformation of yeast and plants.

The bacterium Agrobacterium tumefaciens transforms eukaryotic hosts by transferring DNA to the recipient cell where it is integrated and expressed. Bacterial factors involved in this interkingdom gene transfer have been described, but less is known about host-cell factors. Using the yeast Saccharomyces cerevisiae as a model host, we devised a genetic screen to identify yeast mutants with altered transformation sensitivities. Twenty-four adenine auxotrophs were identified that exhibited supersensitivity to A. tumefaciens-mediated transformation when deprived of adenine. We extended these results to plants by showing that purine synthesis inhibitors cause supersensitivity to A. tumefaciens transformation in three plant species. The magnitude of this effect is large and does not depend on prior genetic manipulations of host cells. These data indicate the utility of yeast as a model for the transformation process and identify purine biosynthesis as a key determinant of transformation efficiency. These findings should increase the utility of A. tumefaciens in genetic engineering.

Agrobacterium tumefaciens↗

PubMed2002

Helicobacter pylori type IV secretion, host cell signalling and vaccine development.

Helicobacter pylori is a bacterial pathogen specialised to colonise and persist the gastric mucosa and to cause severe gastroduodenal disease. A major disease-associated bacterial component is a type IV secretion system (TFSS) encoded by the cytotoxin-associated genes pathogenicity island (cagPAI). Among the multiple responses in H. pylori-infected epithelial cells, the induction of proinflammatory cytokines and chemokines, cell spreading and motility associated with the "hum mingbird" phenotype appear strictly dependent on the functional transporter complex in the cagPAI. H. pylori is also capable of occasionally entering epithelial cells and manipulates the host immune system for immune evasion. Attached bacteria actively translocate the CagA protein into epithelial cells by a TFSS-dependent process and translocated CagA undergoes tyrosine phosphorylation in the carboxy terminal EPIYA sequence repeat motif (Y-972) by kinases of the Src family. Furthermore, we have identified a novel TFSS in H. pylori involved in horizontal DNA-transfer. Host cell signalling events and cellular phenotypes provoked by the cagPAI, the investigation of mechanisms related to gastric cancer as well as the development of a Salmonella based live recombinant vaccine are in the focus of additional departmental activities.

Amino Acid Motifs↗

PubMed1986

Manipulation of graft-versus-host disease for a graft-versus-leukemia effect after allogeneic bone marrow transplantation in AKR mice with spontaneous leukemia/lymphoma.

Graft-versus-host (GVH) disease can result in a beneficial graft-versus leukemia (GVL) effect after bone marrow transplantation in patients with malignant disease. In this report, we used bacteria-free AKR (H-2k) mice bearing advanced spontaneous T cell leukemia/lymphoma as a moel to evaluate the GVH and GVL effects of bone marrow transplantation using fully incompatible SJL (H-2s) donors. A therapeutic GVL effect, accompanied by increased leukemia-free survival, was obtained only when 0.5 X 10(6) allogeneic lymphocytes (lymph node cells) were added to the marrow inoculum. Transplantation of allogeneic bone marrow without added lymph node cells (or use of syngeneic cells) resulted in a significant increase in leukemia relapse; increasing the dose of allogeneic lymph node cells to 2.0 X 10(6) resulted in significantly higher GVH-associated mortality. Survival and therapeutic benefits were obtained only when the intensity of the GVH reaction was carefully controlled by manipulation of alloreactive lymphocytes present in the marrow. These results suggest, indirectly, that T cell depletion may abolish any GVL effect of marrow transplantation, even if the donor is mismatched with the host at the major histocompatibility complex. The frequency in the spleen of cytotoxic T lymphocytes (CTL) reactive against host alloantigens was estimated using limiting-dilution microcytotoxicity assays at various times after transplantation of allogeneic bone marrow with and without added lymph node cells. The average frequency of CTL was highest in mice that were given marrow plus lymph node cells and tested within the first four weeks after transplantation. The level of CTL activity measured in vitro was dependent on the dose of lymphocytes injected and correlated with both the GVL and GVH effects in vivo. Down-regulation of CTL activity against host, but not third-party, alloantigens in vitro was observed under limiting dilution assay conditions, leading to the suggestion that host-specific regulatory cells may be present in these allogeneic bone marrow chimeras.

Animals↗

PubMed2004

Gastrointestinal parasite and host interactions.

PURPOSE OF REVIEW: The mechanisms responsible for the Th2-mediated immune response to enteric nematode parasites are of interest for several reasons. First, intestinal parasites continue to be a major worldwide health issue. Second, the low incidence of parasite infection in industrial nations is cited as a factor in the increased prevalence of proinflammatory-based pathologies. Third, a seemingly paradoxical protection against Th2-mediated allergic reactions is afforded by helminth infection. This review focuses on studies that use enteral parasitic infections as a tool to investigate the functional consequences of upregulation of Th2-mediated immunity and that manipulate host-parasite interactions in an effort to identify mechanisms that can be exploited as potential therapeutic targets. RECENT FINDINGS: Enteric helminth infection improved indices of inflammatory bowel disease in humans and murine models and diminished the allergy-induced changes in pulmonary function. There are emerging or enlarged roles for interleukin-10, interleukin-18, interleukin-9, chemokines, activation of nuclear factor-kappabeta, and factors that alter host resistance in the development of host immunity, and for interleukin-13Ralpha2 receptor in downregulating Th2 responses. As part of the growing appreciation for the contribution of nonimmune cells to parasite-induced changes in intestinal function, studies show that Th2 cytokines exert Stat6-dependent effects that promote worm expulsion. SUMMARY: Further insight into the nature of host-parasite interactions, identification of the pathways and critical mediators that contribute to host resistance, identification of the factors that modulate susceptibility to infection, and the impact of enteric parasites on intestinal function hold much promise for development of novel therapeutic interventions.

Journal Article↗

PubMed1999

Sex allocation and clutch size in parasitoid wasps that produce single-sex broods.

The parasitoid wasp genus Achrysocharoides (Eulophidae) is unusual in that many of its species lay male and female eggs in single-sex clutches. The average clutch size of female broods is always greater than that of male broods, and in some species male clutch size is always one. We constructed models that predicted that severely egg-limited wasps should produce equal numbers of male and female eggs while severely host-limited wasps should produce equal numbers of male and female broods (and hence an overall female-biased sex ratio). Theory is developed to predict clutch size and sex ratio across the complete spectrum of host and egg limitation. A comparison of 19 surveys of clutch composition in seven species of Achrysocharoides showed a general pattern of equal numbers of male and female broods with a female-biased sex ratio (suggesting host limitation) although with considerable heterogeneity amongst collections and with a number of cases of unexpectedly low frequencies of male broods. Using a previous estimate of the relationship between fitness and size in the field, we predicted the maximally productive (Lack) clutch size for female broods of Achrysocharoides zwoelferi to be three. Of clutches observed in nature, 95% were equal to or smaller in size than the predicted Lack clutch size. When we manipulated local host density in the field, and as predicted by our models, clutch size and the proportion of female broods of A. zwoelferi decreased as hosts became more common, but the absolute frequency of male clutches was lower than expected. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed1997

Bacteriophage T4 development depends on the physiology of its host Escherichia coli.

Several parameters of phage T4 adsorption to and growth in Escherichia coli B/r were determined. All changed monotonously with the bacterial growth rate (mu), which was modified by nutritional conditions. Adsorption rate was faster at higher mu values, positively correlated to cell size, and increased by pretreatment with low penicillin (Pn) concentrations; it was directly proportional to total cellular surface area, indicating a constant density of T4 receptors on cell envelopes irrespective of growth conditions. Parameters of phage development and cell lysis were mu-dependent. The rate of phage release and burst size increased, while the eclipse and latent periods decreased with increasing mu. Differentiation between the contribution of several physiological parameters to the development of T4 was performed by manipulating the host cells. A competitive inhibitor of glucose uptake, methyl alpha-D-glucoside, was exploited to reduce the growth rate in the same effective carbon source. Synchronous cells were obtained by the "baby-machine' and large cells were obtained by pretreatment with low Pn concentrations. Lysis was delayed by superinfection, and DNA content and concentration were modified by growing a thy mutant in limiting thymine concentrations. The results indicate that burst size is not limited by cell size or DNA composition, nor directly by the rate of metabolism, but rather by the rates of synthesis and assembly of phage components and by lysis time. The rates of synthesis and assembly of phage components seem to depend on the content of the protein-synthesizing system and lysis time seems to depend on cellular dimensions.

Adsorption↗

PubMed2006

Transactivator of transcription from HIV type 1 subtype E selectively inhibits TNF gene expression via interference with chromatin remodeling of the TNF locus.

The transactivator of transcription (Tat) protein is essential for efficient HIV type 1 (HIV-1) replication and is involved in the transcriptional regulation of the host immune response gene, TNF. In this study, we demonstrate that Tat proteins from representative HIV-1 subtype E isolates, but not from subtypes B or C, selectively inhibit TNF gene transcription and protein production in CD4(+) Jurkat T cells. Strikingly, we show that this repression is due to a tryptophan at residue 32 of Tat E and is secondary to interference with recruitment of the histone acetyltransferase P/CAF to the TNF promoter and with chromatin remodeling of the TNF locus. This study presents a novel mechanism by which HIV-1 manipulates a host immune response gene that is important in its own replication. Moreover, these results demonstrate a new mechanism by which the TNF gene is regulated via chromatin remodeling secondary to viral infection.

Acetylation↗

PubMedDate not supplied

Cancer cachexia.

Cancer cachexia describes a syndrome of progressive weight loss, anorexia, and persistent erosion of host body cell mass in response to a malignant growth. Although often associated with preterminal patients bearing disseminated disease, cachexia may be present in the early stages of tumor growth before any signs or symptoms of malignancy. A decline in food intake relative to energy expenditure (which may be increased, normal, or decreased) is the fundamental physiologic derangement leading to cancer-associated weight loss. In addition, abnormalities of host carbohydrate, protein, and fat metabolism lead to continued mobilization and ineffective repletion of host tissue, despite adequate nutritional support. Mediators of cancer anorexia and associated abnormalities are unknown. Cachectin/TNF or other host-derived cytokines (produced as a defense against malignancy) have been implicated as signal molecules in cachexia, based upon similar metabolic derangements produced by these cytokines in other chronic wasting illnesses. Nutritional support is effective in maintaining body weight of cachectic cancer patients, but ineffective in maintaining lean body mass. Although in one study parenteral nutritional support has improved operative morbidity and mortality in cancer patients, it has not yet improved response to chemotherapy or radiation therapy. Because of metabolic derangements seen in cancer cachexia, effective nutritional treatment regimens will probably require manipulation of host intermediary metabolism in addition to feeding. Insulin therapy or exercise are two such methods which appear to preserve host composition by preferential feeding of the host at the expense of the tumor. Future studies which more clearly define the role of signal molecules in producing cancer cachexia syndrome may lead to new treatment strategies, possibly involving modulation of the effects of such molecules on host metabolism.

Anorexia↗

PubMed1989

Qinghaosu, dietary vitamin E, selenium, and cod-liver oil: effect on the susceptibility of mice to the malarial parasite Plasmodium yoelii.

Young female mice were fed torula-yeast-based diets deficient in vitamin E or selenium or supplemented with cod-liver oil to determine the effect of host antioxidant status on the therapeutic efficacy of the Chinese traditional antimalarial drug qinghaosu (QHS), a sesquiterpene endoperoxide. Vitamin E deficiency enhanced the antimalarial action of QHS against Plasmodium yoelii, both in terms of decreased parasitemia and improved survival but Se deficiency did not. A vitamin E-deficient diet containing 5% cod-liver oil had such strong antimalarial activity in itself that no additional therapeutic benefit of QHS could be demonstrated. Hematocrit values in parasitized mice treated with QHS or fed the cod-liver-oil-supplemented, vitamin E-deficient diet were normal. Nutritional manipulation of host antioxidant status may provide a promising prophylactic and/or therapeutic tool for the control of malaria.

Animals↗

PubMed2003

Subversion of the chemokine world by microbial pathogens.

It is well known that microbial pathogens are able to subvert the host immune system in order to increase microbial replication and propagation. Recent research indicates that another arm of the immune response, that of the chemokine system, is also subject to this sabotage, and is undermined by a range of microbial pathogens, including viruses, bacteria, and parasites. Currently, it is known that the chemokine system is being challenged by a number of mechanisms, and still more are likely to be discovered with further research. Here we first review the general mechanisms by which microbial pathogens bypass mammalian chemokine defences. Broadly, these can be grouped as viral chemokine interacting proteins, microbial manipulation of host chemokine and chemokine receptor expression, microbial blockade of host chemokine receptor signalling, and the largely hypothetical mechanisms of microbial enhancement of host anti-chemokine networks (including digestion, antagonism, and neutralisation of host chemokines and chemokine receptors). We then discuss the potential results of these interactions in terms of outcome of infection.

Animals↗

PubMed2004

Mesenchymal stem cells in autoimmune disease.

Autoimmune diseases afflict more than 3% of the U.S. population. Current therapy for mild to moderate cases is symptomatic, however advanced cases suffer high morbidity and mortality. Advanced patients have benefited from stem cell therapy in the form of bone marrow transplantation in conjunction with high-dose cytotoxic therapy. Broader application of stem cell therapy requires better understanding of how adult stem cells affect development and foster treatment of autoimmune pathologies, and of better ways to manipulate the host immune responses. While extensive research documents the role of hematopoietic stem cells (HSCs) in autoimmune disease, few studies have addressed if and how mesenchymal stem cells (MSCs) contribute to their etiopathology. Recent characterization of MSCs and their role in hematopoiesis and immune modulation suggest that their potential for cell therapy extends beyond their traditional accessory function in HSC engraftment. MSCs contribute significantly to tissue restructuring and immune functioning, in addition to facilitating durable, long-lasting stem cell engraftment. MSCs are relatively easy to obtain and expand in in vitro cultures, rendering them a prime candidate for genetic manipulations for stem cell therapy. They have the potential to differentiate into multiple lineages such as osteoblasts, adipose tissue, cartilage, tendon, and stromal cells. The role of MSCs for autoimmune disease therapy could thus be based both on immune function modulation and contribution to hematopoiesis. In this review, we examine the biology of MSCs, and their potential for cell therapy of autoimmune disease.

Adipose Tissue↗