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At least 145 records · Page 8Linked to original sources

PubMed2004

Immunity to vacuolar pathogens: what can we learn from Legionella?

Intracellular pathogens can manipulate host cellular pathways to create specialized organelles. These pathogen-modified vacuoles permit the survival and replication of bacterial and protozoan microorganisms inside of the host cell. By establishing an atypical organelle, intracellular pathogens present unique challenges to the host immune system. To understand pathogenesis, it is important to not only investigate how these organisms create unique subcellular compartments, but to also determine how mammalian immune systems have evolved to detect and respond to pathogens sequestered in specialized vacuoles. Recent studies have identified genes in the respiratory pathogen Legionella pneumophila that are essential for establishing a unique endoplasmic reticulum-derived organelle inside of mammalian macrophages, making this pathogen an attractive model system for investigations on host immune responses that are specific for bacteria that establish vacuoles disconnected from the endocytic pathway. This review will focus on the host immune response to Legionella and highlight areas of Legionella research that should help elucidate host strategies to combat infections by intracellular pathogens.

Humans↗

PubMed2006

Meningococcal adhesion suppresses proapoptotic gene expression and promotes expression of genes supporting early embryonic and cytoprotective signaling of human endothelial cells.

Neisseria meningitidis colonizes the human nasopharynx and occasionally causes lethal or damaging septicemia and meningitis. Here, we examined the adherence-mediated signaling of meningococci to human cells by comparing gene expression profiles of human umbilical vein endothelial cells (HUVEC) infected by adherent wild-type, frpC-deficient mutant, or the nonadherent (DeltapilD) N. meningitidis. Pili-mediated adhesion of meningococci resulted in alterations of expression levels of human genes known to regulate apoptosis, cell proliferation, inflammatory response, adhesion and genes for signaling pathway proteins such as TGF-beta/Smad, Wnt/beta-catenin and Notch/Jagged. This reveals that adhering piliated meningocci manipulate host signaling pathways controlling cell proliferation while establishing a commensal relationship.

Apoptosis↗

PubMed2004

Genome sequence of a polydnavirus: insights into symbiotic virus evolution.

Little is known of the fate of viruses involved in long-term obligatory associations with eukaryotes. For example, many species of parasitoid wasps have symbiotic viruses to manipulate host defenses and to allow development of parasitoid larvae. The complete nucleotide sequence of the DNA enclosed in the virus particles injected by a parasitoid wasp revealed a complex organization, resembling a eukaryote genomic region more than a viral genome. Although endocellular symbiont genomes have undergone a dramatic loss of genes, the evolution of symbiotic viruses appears to be characterized by extensive duplication of virulence genes coding for truncated versions of cellular proteins.

Amino Acid Motifs↗

PubMed2026

From Sequential Gland Replacement to Recurrent Gland Coordination: A Comparative Framework for Subventral and Dorsal Oesophageal Gland Effectors Across Plant-Parasitic Nematode Lifestyles.

Plant-parasitic nematodes manipulate host tissues through stylet-secreted gene products synthesised principally in two subventral and one dorsal oesophageal gland. Earlier reviews have catalogued effector repertoires, described feeding-site formation, and explained how individual effectors modify host defence, development, and metabolism. However, the temporal coordination of the gland cells themselves has not been comparatively synthesised across parasitic lifestyles. This review therefore advances a gland-centred, lifestyle-dependent framework. In sedentary endoparasites, available evidence supports a pronounced developmental transition: subventral gland products dominate penetration and migration, whereas dorsal gland products become increasingly important during feeding-site initiation and maintenance. Migratory endoparasites repeatedly penetrate, migrate, and feed without establishing permanent feeding cells; their gland activity is consequently predicted to be recurrent and overlapping rather than a one-way replacement. Ectoparasites likewise require behaviour-dependent coordination during repeated probing and external feeding, although direct gland localisation evidence remains limited. We integrate gland origin, secretion chemistry, infection stage, and parasitic behaviour across root-knot, cyst, citrus, false root-knot, lesion, burrowing, and ectoparasitic nematodes. The synthesis distinguishes experimentally demonstrated gland localisation from evidence-weighted inference and formulates testable predictions for comparative gland transcriptomics, spatial expression, and functional silencing. This framework also identifies gland activation, secretion, and stage-critical products as targets for RNA interference, genome editing, resistance breeding, and sustainable nematode management. The principal novelty is therefore not another catalogue of nematode effectors, but a comparative model explaining when and why subventral and dorsal glands exchange, retain, or alternate their functions across contrasting parasitic lifestyles.

dorsal gland↗

PubMed2005

gC1q receptor ligation selectively down-regulates human IL-12 production through activation of the phosphoinositide 3-kinase pathway.

gC1qR, a complement receptor for C1q, plays a pivotal role in the regulation of inflammatory and antiviral T cell responses. Several pathogens, including hepatitis C virus, exploit gC1qR-dependent regulatory pathways to manipulate host immunity. However, the molecular mechanism(s) of gC1qR signaling involved in regulating inflammatory responses remains unknown. We report the selective inhibition of TLR4-induced IL-12 production after cross-linking of gC1qR on the surface of macrophages and dendritic cells. Suppression of IL-12 did not result from increased IL-10 or TGF-beta, but was dependent on PI3K activation. Activation of PI3K and subsequent phosphorylation of Akt define an intracellular pathway mediating gC1qR signaling and cross-talk with TLR4 signaling. This is the first report to identify signaling pathways used by gC1qR-mediated immune suppression, and it establishes a means of complement-mediated immune suppression to inhibit Th1 immunity crucial for clearing pathogenic infection.

Animals↗

PubMed1979

Temporary disappearance ("eclipse") of LPC-1 plasmacytoma M component synthesis following tumor cell transfer.

The early phase of LPC-1 plasmacytoma development was studied by in vivo labeling with [6-14C]arginine using its M component (immunoglobulin G 2a,kappa) as marker. At a time when M component was not detected or faint by protein staining of electrophoretograms, significant labeling of M component was detectable by autoradiography. Labeling of the M component was fairly constant for the first 10 hr but was markedly decreased from Days 1 to 7. Nadir (0 to 3% of initial 30-min value) was observed on Day 3. Recovery of M component labeling to the 30-min level was complete by Day 13. This period of marked reduction or "eclipse" in newly synthesized M component was shortened by 2 days when mice were pretreated with pristane or cyclophosphamide prior to tumor cell transfer. The eclipse period was also 2 days shorter in athymic BALB/c-nu/nu mice than in normal BALB/c mice. The eclipse period corresponds to the classical "lag" following tumor cell transfer before tumor growth can be detected by conventional methods. The sensitivity of the [6-14C]arginine pulse permits the in vivo detection of small numbers of tumor cells (as few as 10(6) cells) over the early time periods after cell transfer. Modification of eclipse by manipulating host and/or tumor cells may elucidate the accompanying cellular and biochemical events.

Animals↗

PubMedDate not supplied

Residual immunogenicity of irradiated spleen cell suspensions after a single intravenous injection of sheep red blood cells in mice.

Studies were carried out to characterize the residual immunogenicity located in spleen cells of mice after one single intravenous injection of SRBC. An in vivo system was applied for initiation and expression of the immune response consisting of one intraperitoneally injection of spleen cell suspension from SRBC-injected mice in separate groups of recipients in which DTH and secondary humoral response were measured, respectively: six days or four days after the transfer of irradiated spleen cell suspension, the separate groups of recipients being either pretreated with cyclophosphamide (200 mg/kg) or primed with 5 X 10(5) SRBC. The residual immunogenicity was found to be located in a population of radio-resistant (10,000 rads) adherent spleen cells. The same population derived from naive mice injected together with the native antigen did not modify the immune response as compared with those induced by the antigen alone. Furthermore, irradiated spleen cell suspensions from SRBC-injected mice were not able to transfer adoptively DTH sensitivity in naive recipients. Accordingly to the test used to evaluate the residual immunogenicity, it was found that the kinetics of residual immunogenicity able to induce DTH was different from those which stimulate the secondary humoral response. Furthermore, it was found that distinct variations of residual immunogenicity for DTH and antibody formation were induced by varying host manipulations, such as non-specific stimulation of the reticulo-endothelial system, specific activation of T cells involved in DTH or helper function or induction of a state of anergy. It appears, therefore, that the same population of radio-resistant adherent spleen cells are able to induce an immune response and to dispatch information to cells involved in DTH or those involved in antibody synthesis. Moreover, depending upon conditions of immunization, varying subsets of T cells are able to modify the dispatching function of these cells in the processing or presentation of antigen to committed or non-committed lymphocytes.

Animals↗

PubMed2004

Intra-specific host sharing in the manipulative parasite Acanthocephalus dirus: does conflict occur over host modification?

The acanthocephalan parasite Acanthocephalus dirus induces a colour change in the intermediate host, the aquatic isopod Caecidotea intermedius, which increases transmission to definitive hosts (creek chub, sunfish). We examined the potential for conflict to occur between infective (cystacanth) and non-infective (acanthor, acanthella) stages of A. dirus over the level of colour modification that should be induced when these stages share a host. Using a field survey, we showed that host sharing by infective and non-infective stages was relatively common and that infective and non-infective stages differed in their effects on colour modification. Non-infective stages induced a colour change over 40% of the body, whereas infective stages induced a colour change over 80%. Thus, conflict could occur between stages over the level of modification that should be induced. We then showed that mixed-stage infections induced a colour change in the host that was consistent with the level of modification induced by the infective stage. We discuss the potential significance of these results to patterns of host modification and their effects on stage-related survival in nature.

Acanthocephala↗

PubMed2001

Amplification of engrafted hepatocytes by preparative manipulation of the host liver.

Scarcity of donor livers is a major obstacle to the general application of hepatocytes for the development of bioartificial liver assist devices as well as intracorporeal engraftment of hepatocytes for the treatment of inherited metabolic diseases. The number of hepatocytes that can be transplanted into the liver safely in a single sitting also limits the utility of this procedure. These limitations could be addressed by providing preferential proliferative advantage to the transplanted cells. Studies using transgenic mouse recipients or donors have indicated that massive repopulation of the host liver by engrafted hepatocytes requires that the transplanted cells are subjected to a proliferative stimulus to which the host hepatocytes cannot respond. Prevention of host hepatocyte proliferation has been achieved by treatment with a plant alkaloid, retrorsine. Because retrorsine is carcinogenic, we have evaluated preparative irradiation for this purpose. The proliferative stimulus may consist of the loss of hepatic mass (e.g., partial hepatectomy, reperfusion injury or induction of Fas-mediated apoptosis by gene transfer) or administration of stimulants of hepatocellular mitosis (e.g., growth factors or thyroid hormone). Potential applications of these preparative manipulations of the host liver include the treatment of inherited metabolic disorders by transplantation of allogeneic hepatocytes, hepatocyte-mediated ex vivo gene therapy, rescuing liver cancer patients from radiation-induced liver damage, and expansion of human hepatocytes in animal livers.

Animals↗

PubMed1984

Alterations of physical and biochemical parameters of the R3327-CP rat prostate adenocarcinoma following hormonal manipulation of the host.

Several physical and biochemical parameters of a rapidly growing, hormonally responsive, poorly differentiated strain of Dunning R3327 rat prostatic adenocarcinoma (the CP strain) were monitored for 1 month during growth in control and hormonally manipulated male Fischer X Copenhagen rats. The tumor was implanted into control rats and into rats 1 month following orchiectomy. Twenty-nine days following tumor implantation, 1 group of unoperated rats was orchiectomized while the rats implanted subsequent to orchiectomy were repleted with pharmacological doses of testosterone. At 2 and 4 weeks following treatment, half the original number of rats from each group were sacrificed and the growth rate (doubling time), per cent of aneuploid cells and androgen receptor levels (total, cytoplasmic and nuclear) were determined for each tumor. Orchiectomy increased tumor doubling time, while testosterone repletion decreased it, demonstrating the hormonal dependence of this tumor strain. Orchiectomy also decreased the levels of aneuploid cells in the tumor; however, repletion of testosterone to rats orchiectomized prior to implantation did not restore the aneuploid cell number to control levels. A sensitive indicator of the hormonal status of the tumor was the per cent of androgen receptors in the nucleus. Tumors grown in rats orchiectomized after implantation had the lowest percentage of androgen receptor in the nucleus while orchiectomized rats repleted with testosterone had the highest percentage. Comparison of the levels of androgen receptors in the tumors from the various groups (androgen receptor per gram of tissue) unexpectedly revealed that tumors grown in the orchiectomized rats had slightly higher total receptor levels than did control tumors, while the tumors of orchiectomized rats repleted with testosterone had lower amounts than did the control tumors. In contrast to these findings, the prostates of orchiectomized rats replenished with testosterone had higher levels of total androgen receptor than did the prostates of control rats.

Adenocarcinoma↗

PubMed2005

Mycobacterial manipulation of the host cell.

Phagosome biogenesis, the process by which macrophages neutralize ingested pathogens and initiate antigen presentation, has entered the field of cellular mycobacteriology research largely owing to the discovery 30 years ago that phagosomes harboring mycobacteria are refractory to fusion with lysosomes. In the past decade, the use of molecular genetics and biology in different model systems to study phagosome biogenesis have made significant advances in understanding subtle mechanisms by which mycobacteria inhibit the maturation of its phagosome. Thus, we are beginning to appreciate the extent to which these pathogens are able to interfere with innate immune responses and manipulate defense mechanisms to enhance their survival within the human host cell. Here, we summarize current knowledge about phagosome maturation arrest in infected macrophages and the subsequent attenuation of the macrophage-initiated adaptive anti-mycobacterial immune defenses.

Humans↗

PubMedDate not supplied

A syngeneic metastatic tumor model in mice: the natural immune response of the host and its manipulation.

The cell-mediated immune response against a transplantable syngeneic metastatic solid tumor in mice was studied. The immune reactivity of spleen cells from tumor-bearing mice was found to vary during development of the tumor. For about a week after tumor transplantation, the spleen cells were able to protect recipient mice against challenge with tumor cells. Subsequently, the protective activity was replaced by an enhancing activity. Recipient mice that received tumor cells together with spleen cells from mice bearing tumors for about two or three weeks had a higher incidence of tumor takes and larger tumors than controls. This enhancement of tumor development was correlated with the size of the local tumor or metastases in the donors. The enhancing activity was found to be mediated by T lymphocytes and appeared to suppress the protective immune response of the recipients. We devised a system to strengthen the immune response of the host against the development of tumor metastases. In the tumor model used, removal of the local tumor after s.c. transplantation failed to prevent the development of lung metastases and death in most of the mice. However, syngeneic spleen cells which had been sensitized in vitro against tumor cells were found to serve as immunotherapeutic agents. Injection of such spleen cells into mice from which primary tumor implants had been removed surgically led to a markedly increased survival. Spleen cells from both normal and tumor-sensitized donors were effective, but splenocytes from mice bearing large tumors did not reduce metastatic development after sensitization in vitro. Thus, protection against the development of lethal metastases can be achieved with certain types of lymphocytes sensitized in vitro.

Animals↗

PubMed2005

Manipulation of the host actin cytoskeleton by Salmonella--all in the name of entry.

The invasive pathogen Salmonella enterica has evolved sophisticated mechanisms to subvert the cytoskeletal machinery of its host. Following contact with the host cell, it delivers a distinct arsenal of effector proteins directly into the cytoplasm. These bacterial effectors coordinate transient actin rearrangements and alter vesicle trafficking to trigger invasion, without causing overt cellular damage. Recent studies have shed new light on the signaling mechanisms underlying this remarkable host-pathogen interface, in particular, highlighting the unique multi-functional role and temporal regulation of key bacterial effectors.

Actins↗

PubMed2002

A pox on thee! Manipulation of the host immune system by myxoma virus and implications for viral-host co-adaptation.

The poxviruses have evolved a diverse array of proteins which serve to subvert innate and adaptive host responses that abort or at least limit viral infections. Myxoma virus and its rabbit host are considered to represent an ideal poxvirus-host system in which to study the effects of these immunomodulatory proteins. Studies of laboratory rabbits (Oryctolagus cuniculus) infected with gene knockout variants of myxoma virus have provided compelling evidence that several myxoma virus gene products contribute to the pathogenic condition known as myxomatosis. However, myxomatosis, which is characterized by skin lesions, systemic immunosuppression, and a high mortality rate, does not occur in the virus' natural South American host, Sylvilogus brasiliensis. Moreover, in Australia where myxoma virus was willfully introduced to control populations of O. cuniculus, myxomatosis-resistant rabbits emerged within a year of myxoma virus introduction into the field. In this review I discuss the characterized immunomodulatory proteins of myxoma virus, their biochemical properties, their pathogenic effects in laboratory rabbits, the role of the host immune system in the susceptibility or resistance to myxomatosis, and the evidence that immunomodulatory genes may have been attenuated during the co-adaptation of myxoma virus and O. cuniculus in Australia.

Adaptation, Physiological↗

PubMed1998

Evolution and phylogeny of behavioural manipulation of insect hosts by parasites.

The literature contains many examples of changes induced by parasites in the behaviour and/or other phenotypic traits of insects. From an evolutionary perspective, the nature of these changes is usually difficult to assess. Parasite-induced changes in host behaviour can be adaptations of either host or parasite, or they can be mere pathological consequences of infection. Of the many criteria and experimental tests necessary to distinguish between adaptations and non-selected consequences, two are particularly important: the demonstration of fitness benefits for either host or parasite associated with the behavioural change, and the elucidation of the proximate mechanism responsible for the behavioural change. Another approach can serve to identify adaptive changes in behavior: mapping specific behavioural alterations on a phylogeny of either hosts or parasites. The usefulness of this approach is illustrated with two examples, acanthocephalan-cockroach associations and insect-fungus associations. The adaptive nature of parasite-induced behavioural changes will always be difficult to evaluate because they are the product of two distinct but interacting genotypes. However, experimental and phylogenetic approaches can provide valuable insights into the evolutionary history of insect-parasite interactions.

Acanthocephala↗

PubMed2002

The viral manipulation of the host cellular and immune environments to enhance propagation and survival: a focus on RNA viruses.

Virus infection presents a significant challenge to host survival. The capacity of the virus to replicate and persist in the host is dependent on the status of the host antiviral defense mechanisms. The study of antiviral immunity has revealed effective antiviral host immune responses and enhanced our knowledge of the diversity of viral immunomodulatory strategies that undermine these defences. This review describes the diverse approaches that are used by RNA viruses to trick or evade immune detection and response systems. Some of these approaches include the specific targeting of the major histocompatibility complex-restricted antigen presentation pathways, apoptosis, disruption of cytokine function and signaling, exploitation of the chemokine system, and interference with humoral immune responses. A detailed insight into interactions of viruses with the immune system may provide direction in the development of new vaccine strategies and novel antiviral compounds.

Adult↗

PubMed2004

Structural insights into bacterial modulation of the host cytoskeleton.

Many bacterial pathogens manipulate the host cell cytoskeleton during infection. Such cytoskeletal modulation can occur at several points of contact between the pathogen and the host, and involves extracellular receptors, intracellular signal transduction and cytoskeletal proteins themselves. The field of bacterial pathogenesis has progressed dramatically over the past decade, such that structural knowledge is both timely and essential for a full appreciation of the biology at the pathogen-host interface. Several recent examples involving bacterial proteins that target actin, Rho family GTPases and extracellular receptors have contributed to a structural understanding of eukaryotic cytoskeletal modulation by pathogens.

Animals↗

PubMed1998

Exploitation of manipulators: 'hitch-hiking' as a parasite transmission strategy.

For many parasites with complex life cycles, manipulation of host behaviour is an adaptation to increase the probability of successful transmission. Since manipulation is likely to be costly, other parasites may exploit hosts already manipulated so as to ensure their transmission without investing in manipulation. Such a cheating strategy, called 'hitch-hiking', could be adaptive in a range of situations. We first propose and discuss criteria that should be met by any parasite to be considered a hitch-hiker. Then, to understand the evolution of the hitch-hiking strategy, we use simple mathematical models to analyse the influence of several variables on the potential benefits for a nonmanipulative parasite of actively seeking a ride to the definitive host with a manipulative parasite. The models suggest that the prevalence or abundance of manipulative parasites will be a key determinant of whether hitch-hiking can be an advantageous option for other parasites. Copyright 1998 The Association for the Study of Animal Behaviour.

Journal Article↗