PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “host manipulation”

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

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

At least 181 records · Page 10Linked to original sources
PubMed2006

'Suicide' of crickets harbouring hairworms: a proteomics investigation.

Despite increasing evidence of host phenotypic manipulation by parasites, the underlying mechanisms causing infected hosts to act in ways that benefit the parasite remain enigmatic in most cases. Here, we used proteomics tools to identify the biochemical alterations that occur in the head of the cricket Nemobius sylvestris when it is driven to water by the hairworm Paragordius tricuspidatus. We characterized host and parasite proteomes during the expression of the water-seeking behaviour. We found that the parasite produces molecules from the Wnt family that may act directly on the development of the central nervous system (CNS). In the head of manipulated cricket, we found differential expression of proteins specifically linked to neurogenesis, circadian rhythm and neurotransmitter activities. We also detected proteins for which the function(s) are still unknown. This proteomics study on the biochemical pathways altered by hairworms has also allowed us to tackle questions of physiological and molecular convergence in the mechanism(s) causing the alteration of orthoptera behaviour. The two hairworm species produce effective molecules acting directly on the CNS of their orthoptera hosts.

Amino Acid Sequence↗
PubMed1995

Effects of dietary lipid manipulation upon graft vs host and host vs graft responses in the rat.

The popliteal lymph node (PLN) assay was used to establish whether dietary lipids with differing fatty acid compositions could affect cell-mediated immunity in the rat. Weanling rats were fed for 4 weeks on a lowfat (2.5% by weight; LF) diet or on diets containing 20% (by weight) hydrogenated coconut oil (HCO), olive oil (OO), safflower oil (SO), evening primrose oil (EPO), or menhaden (fish) oil (MO). Feeding the MO diet suppressed the graft vs host response compared with feeding the LF, HCO, SO, or EPO diets, while feeding the OO diet suppressed this response compared with feeding the LF or EPO diets. Feeding the MO diet suppressed the host vs graft response compared with feeding each of the other diets. Following the graft vs host reaction, PLN lymphocytes from animals fed the MO diet had significantly lower levels of expression of LFA-1 and CD2 compared with PLN lymphocytes from animals fed the LF diet; furthermore, they had lower levels of expression of T-cell receptor (TcR), CD4, CD8, LFA-1, and CD2 compared with lymphocytes from animals fed some, and in the case of CD2 each, of the other high-fat diets. Feeding the MO diet resulted in a lower proportion of cells expressing the interleukin-2 receptor, indicating an inhibition of lymphocyte activation, and a lower proportion of CD16+/CD3- cells, indicating a decrease in the proportion of NK cells within the PLN. Following the host vs graft reaction, PLN lymphocytes from animals fed the MO diet had significantly lower levels of expression of TcR and CD8 compared with lymphocytes from animals fed each of the other diets; furthermore, they had lower levels of expression of CD4, CD2, and LFA-1 compared with lymphocytes from animals fed the LF, HCO, OO, or SO diets. These observations indicate that the smaller PLN size of animals fed the MO diet results from an inhibition of activation and subsequent proliferation of cells within the node and perhaps also a suppression of movement of cells from the bloodstream to the PLN, due to decreased level of expression of adhesion molecules. These lowered levels of expression might be due to an inhibitory effect of the n-3 polyunsaturated fatty acids found in MO upon components of the signal transduction pathways involved in lymphocyte activation or upon expression of the genes for the surface molecules or both.

Animals↗
PubMed1992

Pharmacologic manipulation of graft versus host induced splenomegaly.

A murine graft versus host (GVH) model was developed as a tool for drug discovery. A pharmacological survey revealed that as a class the anti-rheumatics (e.g., auranofin, azathioprine, and methotrexate) were the most potent inhibitors of GVH induced splenomegaly. The immunosuppressants, cyclophosphamide and cyclosporine A, and the glucocorticoids (e.g., dexamethasone, hydrocortisone, and corticosterone) were all able to suppress the GVH response. Anti-inflammatory agents (e.g., indomethacin and piroxicam), and a series of central nervous system affecting drugs, including serotonin agonists (e.g., trifluromethylphenylpiperazine (tfMPP), 1-(3-chlorophenyl)piperazine (mCPP), and quipazine), and tricyclic antidepressants (e.g., amitriptyline, desipramine, imipramine, and nortriptyline) typically were ineffective at doses up to 10 mg/kg. However, at high dose levels (30 mg/kg) piroxicam enhanced while amitriptyline and cyproheptadine (a mixed serotonin and histamine antagonist) suppressed GVH induced splenomegaly. These data provide a pharmacological profile for a series of immunomodulator, anti-inflammatory, and central nervous system active compounds in a classic immunologic model.

Animals↗
PubMed2003

Ura- host strains for genetic manipulation and heterologous expression of Torulaspora delbrueckii.

Recently, the industrial and academic interest in the yeast Torulaspora delbrueckii has increased notably due to its high resistance to several stresses. This characteristic has made of this organism a very attractive model to study the molecular basis of the stress response in yeast. However, very little is known about the physiology and genetics of this yeast, and the tools for its manipulation have not been developed. Here, we have generated Ura(-) strains of the baker's yeast T. delbrueckii IGC5323 by either 5-FOA-aided selection or transformation with a PCR-based disruption cassette, natMX4, which confers nourseothricin resistance. Furthermore, the mutant and disruptant strains were used as recipient of a plasmid containing the xlnB cDNA from Aspergillus nidulans. Our results indicate that Torulaspora transformants produce active recombinant protein at a similar level to that found for Saccharomyces.

Gene Expression Regulation, Fungal↗
PubMed2003

Manipulation of the vertebrate host's testosterone does not affect gametocyte sex ratio of a malaria parasite.

Gametocyte sex ratio of the malaria parasite Plasmodium mexicanum is variable in its host, the western fence lizard (Sceloporus occidentalis), both among infections and within infections over time. We sought to determine the effect of host physiological quality on the gametocyte sex ratio in experimentally induced infections of P. mexicanum. Adult male lizards were assigned to 4 treatment groups: castrated, castrated + testosterone implant, sham implant, and unmanipulated control. No significant difference in gametocyte sex ratio was found among the 4 treatment groups. Two other analyses were performed. A surgery stress analysis compared infection sex ratio of castrated, castrated + testosterone implant, and sham implant groups with the unmanipulated control group. A testosterone alteration analysis compared infection sex ratio of the castrated and castrated + testosterone implant groups with the sham implant and unmanipulated control groups. Again, no significant difference was observed for these 2 comparisons. Thus, physiological changes expected for experimentally induced variation in host testosterone and the stress of surgery were not associated with any change in the gametocyte sex ratio. Also, theex-periment suggests testosterone is not a cue for shaping the sex ratio of gametocytes in P. mexicanum. These results are related to the evolutionary theory of sex ratios as applied to malaria parasites.

Animals↗
PubMed1997

From the natural evolution to the genetic manipulation of the host-range of retroviruses.

The discovery that retroviruses share many features with retrotransposons led to the proposal that retroviruses evolved from cellular movable elements and became independent genetic entities, which started a parasitic life on their own. It has been further hypothesized that in the course of this evolutionary process, retrotransposons incorporated a cellular membrane glycoprotein gene into their genome, which finally became the envelope gene of the virus. Equipped with a error-prone polymerase and a high recombination rate during replication, the resulting genetic element has been equipped with a powerful machinery to change and modify itself, in particular the envelope gene, not only to escape the immune system, but also to change the host species. The HIV-1 epidemiology may serve as the best example of this still on-going evolutionary process. Since retroviruses insert their genome into that of the host cell as part of their life cycle, they have been extensively utilized as gene transfer vectors (retroviral vectors). Recently, experiments have been initiated to modify the envelope of retroviral vectors in the laboratory to alter the host range for specific gene transfer applications. This review highlights aspects of the natural evolution and the genetic modification of the retroviral envelope protein. Its implication on the safety of retroviral vectors in human gene therapy is also discussed.

Animals↗
PubMed2006

Interactions of human retroviruses with the host cell cytoskeleton.

As obligate cell parasites, viruses have evolved into professional manipulators of host cell functions. Accordingly, viruses often remodel the cytoskeleton of target cells in order to convert one of the cell's barriers to viral replication into a vehicle for the virus that facilitates the generation of infectious progeny. Surprisingly little is known about the mechanisms employed by two major human pathogens, HIV and human T-cell leukaemia virus (HTLV), to exploit host cell cytoskeletal dynamics. New studies have begun to unravel how these retroviruses remodel cytoskeletal structures to facilitate entry into, transport within and egress from target cells. Exciting progress has been made in understanding how HIV and HTLV polarize actin and also control microtubule organization to spread from donor to target cells in close cell-contacts termed virological synapses.

Biological Transport↗
PubMed1980

Tumor growth in experimental animals: nutritional manipulation and chemotherapeutic response in the rat.

The effects of nutritional manipulation on host body weight dynamics, tumor growth patterns and host-tumor responses to chemotherapy were studied in Sprague-Dawley rats with Walker-256 carcinosarcomas. Group I maintained throughout on a regular diet (RD) gained carcass weight steadily. Group II lost carcass weight while fed a protein-free diet (PFD) but rapidly gained weight after switching to RD on day 15. Mean tumor volume increased 105% in Group I from day 15 to 21, 218% in Group II and 77% in Group III (continued on PFD p less than 0.05). From day 21 to day 33 tumor growth patterns were similar in Groups I and II, while mean tumor volume eventually plateaued in Group III. In Study B, Group II animals were given Methotrexate (MTX-20 mg/kg) two days and six days after switching from PFD to RD. The mean change in tumor volume in the MTX-treated rats was 1.31 +/- 0.1 cm3 compared with 8.14 +/- 0.1 cm3 (p less than 0.001) in the saline-treated control rats. MTX did not significantly affect tumor growth patterns in Group III (PFD) rats. In Study A, protein-calorie malnutrition resulted in host carcass weight loss and tumor growth retardation while nutritional repletion restored host carcass weight and stimulated tumor growth. In Study B, MTX was maximally effective in tumor-bearing rats that were switched from PFD to RD demonstrating that nutritional manipulation can improve host nutritional status and increase tumor response to chemotherapy.

Animals↗
PubMed2004

Modulation of autonomic balance by tumors and viruses.

Autonomic balance, a function generally under host control, is subject to modulation by other signalers. In some cases, modulation of host autonomic function through behavioral and physical stressors exerted by another individual may have negative consequences for the stress recipient by inducing sympathetic bias. Modulation of autonomic function may sometimes benefit one party at the expense of another. Tumors and HIV are examples of illegitimate signalers who may induce host sympathetic bias to promote their own growth and evade host immune surveillance. Paraneoplastic and paraviral syndromes such as hypertrophic osteoarthopathy, QTc prolongation, insomnia, and cachexia could be viewed as epiphenomena related to the tumoral and viral manipulation of host autonomic balance. In a more general framework, other paraneoplastic and paraviral syndromes may represent epiphenomena related to modulation of endocrine, cytokine, and autonomic functions by tumors and viruses to promote their own survival. Spatial distribution of cancers and viruses within the host may reflect affinity for strategic locations that facilitate manipulation of a variety of host functions including autonomic, endocrine, and cytokine regulation. A more general for understanding spatial distribution of diseases based on gradients of autonomic balance in the body are explored. Darwinian perspectives are discussed.

Autonomic Nervous System Diseases↗
PubMed2025

The pathway of autophagy in the epigenetic landscape of Mycobacterium-host interactions.

Macroautophagy (autophagy) is an evolutionarily conserved process that degrades excess cytoplasmic components, such as protein aggregates and damaged organelles, by encapsulating them within double-membrane autophagosomes. These autophagosomes undergo distinct stages - initiation, phagophore nucleation, expansion, and closure - before fusing with lysosomes (or occasionally endosomes) for degradation and recycling. This process is regulated by ATG (autophagy related) proteins, which govern autophagosome formation and lysosomal fusion. Epigenetic modifications and transcription factors can regulate ATG gene expression in the nucleus. Autophagy also plays a key role in eliminating intracellular Mycobacterium tuberculosis (Mtb) through the lytic and antimicrobial activities of autolysosomes, which are more potent antimicrobial compartments than conventional phagosomes. Emerging evidence suggests that Mtb can modify the host epigenome and transcriptional machinery, significantly affecting the host immune response. This review explores the epigenetic regulation of autophagy during mycobacterium-host interactions. The interplay between epigenetic regulation and autophagy highlights a crucial aspect of host-pathogen interactions during Mtb infection. Understanding how Mtb manipulates the host epigenome to regulate autophagy could lead to the development of novel therapeutic strategies that enhance autophagic pathways or counteract Mtb's immune evasion tactics.Abbreviations: AM: Alveolar macrophages; ATG: autophagy related; DNMT: DNA methyltransferase; FOXO3: forkhead box O3; HAT: histone acetyltransferase; HDAC: histone deacetylase; MIR: microRNA; MTOR: mechanistic target of rapamycin kinase; Mtb: Mycobacterium tuberculosis; ROS: reactive oxygen species; SIRT: sirtuin; STPK: serine/threonine protein kinase.

Autophagy↗
PubMed2000

Regression of engineered tumor cells secreting cytokines is related to a shift in host cytokine profile from type 2 to type 1.

The precise role of the endogenous immune response in modulating cancer development remains unclear. In this study, three mouse tumor cell lines were used to elucidate the immune mechanisms for tumor regression versus tumor growth. These cell lines were (1) the poorly immunogenic VKCK cell line and (2) its two derived cell lines VKCK/RM4-tumor necrosis factor-alpha (TNF-alpha) and VKCK/RM4-interferon-gamma (IFN-gamma) engineered to secrete TNF-alpha and IFN-gamma, respectively. Our data showed that VKCK tumors grew aggressively in syngeneic BALB/c mice, and vaccination of irradiated VKCK cells failed to protect the mice from a subsequent challenge with the same tumor. In contrast, engineered VKCK tumor cells lost their tumorigenicity, and vaccination of engineered VKCK cells induced a protective immunity against VKCK cells that was mediated with VKCK-specific CD8+T cells. Susceptible mice developed a Th2-dominant response, whereas resistant mice developed a Th1-dominant response to VKCK. The T cell proliferative response and cytolytic activity against VKCK developed in both resistant and susceptible mice, but in the susceptible mice, these responses were much weaker compared with those in the resistant mice. Our results indicate that regression of tumor cells engineered to secrete cytokines TNF-alpha and IFN-gamma is related to a shift from a host type 2 to a type 1 cytokine profile. Our results further suggest that the failure of unmodified VKCK to generate efficacious T cells is not due to an inability to recognize tumor antigens but, rather, to the nature and magnitude of the antitumor immune response that develops. A better understanding of the mechanisms by which tumor cells modulate the host immune system may result in newer approaches for manipulating host-tumor interactions that favor the development of a protective antitumor immune response.

Animals↗
PubMed1997

Cell proliferation enhances entry of Listeria monocytogenes into intestinal epithelial cells by two proliferation-dependent entry pathways.

Bacterial entry into intestinal host cells is the result of a fairly sophisticated manipulation of host cell machinery by the pathogens. To study further the potential cell target of Listeria spp., the in-vitro entry of L. monocytogenes strains into intestinal cells was examined in relation to the metabolism, proliferation and differentiation of the cells by the alamarBlue assay, [3H] thymidine incorporation, and brush border-associated enzyme activities, respectively. The study showed that cell metabolism was not involved in the entry of L. monocytogenes in three cell models (two human and one porcine). On the other hand, entry was closely related to the proliferation process and poorly related to the differentiation state of the cells. The use of L. monocytogenes mutants lacking invasion proteins showed that InlA and InlB acted in synergy to mediate the entry of L. monocytogenes into proliferative cells, whereas InlA alone seemed to be involved in the entry into non-proliferative cells. These two entry pathways could correspond to the two cellular processes used by L. monocytogenes to enter proliferative and non-proliferative cells, as suggested by the use of cytochalasin D, nocodazole, chloroquine and monodansylcadaverine. Taken together, we propose a hypothesis in which the entry of L. monocytogenes is mediated by interaction between randomly distributed E-cadherin on the surface of proliferative cells. In contrast, the entry into non-proliferative cells may involve pp60c-src, a proto-oncogenic tyrosine kinase signal that modifies E-cadherin localisation. In conclusion, these results suggest that L. monocytogenes may preferentially enter crypt cells in vivo by a microfilament-dependent process, whereas the few bacteria that infect villus cells enter by an E-cadherin-internalin interaction that mediates microtubule-dependent endocytosis.

Animals↗
PubMed2004

Invasion of epithelial mammalian cells by Paracoccidioides brasiliensis leads to cytoskeletal rearrangement and apoptosis of the host cell.

Paracoccidioides brasiliensis (Pb) yeast cells can enter mammalian cells and probably manipulate the host cell environment to favor their own growth and survival. We studied the uptake of strain Pb 18 into A549 lung and Vero epithelial cells, with an emphasis on the repercussions in the cytoskeleton and the apoptosis of host cells. Cytoskeleton components of the host cells, such as actin and tubulin, were involved in the P. brasiliensis invasion process. Cytochalasin D and colchicine treatment substantially reduced invasion, indicating the functional participation of microfilaments (MFs) and microtubules (MTs) in this mechanism. Cytokeratin could also play a role in the P. brasiliensis interaction with the host. Gp43 was recognized by anti-actin and anti-cytokeratin antibodies, but not by anti-tubulin. The apoptosis induced by this fungus in infected epithelial cells was demonstrated by various techniques: TUNEL, DNA fragmentation and Bak and Bcl-2 immunocytochemical expression. DNA fragmentation was observed in infected cells but not in uninfected ones, by both TUNEL and gel electrophoresis methods. Moreover, Bcl-2 and Bak did not show any differences until 24 h after infection of cells, suggesting a competitive mechanism that allows persistence of infection. Overexpression of Bak was observed after 48 h, indicating the loss of competition between death and survival signals. In conclusion, the mechanisms of invasion of host cells, persistence within them, and the subsequent induction of apoptosis of such cells may explain the efficient dissemination of P. brasiliensis.

Animals↗
PubMed2006

Manipulation of dendritic cells for host defence against intracellular infections.

Dendritic cells (DCs) are an important innate immune cell type which is the bridge between innate and adaptive immunity. Mounting experimental evidence suggests that manipulating DCs represents a powerful means to enhance host defence against intracellular infectious diseases. We have developed several strategies to manipulate DCs either in vivo or in vitro for the purpose of enhancing the effect of vaccination or immunotherapeutics. In vivo delivery of transgene encoding GM-CSF (granulocyte/macrophage colony-stimulating factor), a DC-activating cytokine, increases the number and activation status of DCs at various tissue sites and enhances antimicrobial immune responses in murine models. Co-expression or co-delivery of GM-CSF gene transfer vector with an antimicrobial vaccine enhances microbial antigen-specific T-cell responses and immune protection. Murine bone marrow-derived DCs are being manipulated in vitro and exploited as a vaccine delivery system. Transduction of DCs with a virus-vectored tuberculosis vaccine is a powerful way to activate T-cells in vivo. Such genetically modified DC vaccines can be administered either parenterally or mucosally via the respiratory tract.

Adjuvants, Immunologic↗
PubMed1981

New concepts in therapeutic photomedicine: photochemistry, optical targeting and the therapeutic window.

Advances in optics technology, synthetic photochemistry, and the science of photobiology make it possible to think beyond phototherapy and photochemotherapy which is dependent on direct photochemical alteration of metabolites or direct phototoxic insult to cells. This report discusses another gender of photomedicine therapy which includes in vivo photoactivation of medicines, photon-dependent drug delivery, and manipulation of host and exposure source to maximize therapeutic index. These therapeutic manipulations are made possible because the skin is highly overperfused and because non-ionizing electromagnetic radiation that enters skin and blood has adequate photon energy to cause electronic excitation. Radiation of 320-800 nm is not very directly phototoxic, is absorbed by a variety of relatively nontoxic photolabile molecules and has an internal dosimetric depth profile. This radiation can therefore be used to activate, deactivate, bind, release or biotransform medications in vivo in skin or other organs. The photochemist, synthetic chemist and photobiologist can collaborate to significantly increase therapeutic possibilities.

Humans↗
PubMed1988

Cestode transmission patterns.

The paradox of high prevalence but low probability of having an egg develop to an adult has been resolved by the evolution of 3 major and basic strategies involving transmission: evolution of life cycles interpolated into host biology; presentation of infective stages that increase probability of contact between host and parasite; and increase in reproductive potential. The rarity of direct cycles confirms that cycles in themselves, with at least 2 hosts, are a key element of cestode success because they provide a vehicle for dispersal and transmission of infective stages. Transmission is primarily by passive stages that become incorporated through intermediate hosts or accidentally in the food chain. High host specificity results from efficient transmission pathways but may represent a fragile system for the evolution of the species. Probability of transmission is increased through diversity of intermediate hosts, making eggs more susceptible to ingestion and by behavioral manipulation of hosts by parasite stages. Spatial and temporal aspects of transmission may be increased through paratenesis. Asexual proliferation of immature stages is uncommon and is favored where there is selective predation; such proliferation may be part of a transmission strategy of colonial cestodes that require high infrapopulations in order to survive. Hyperapolysis may be part of a transmission strategy used by the Tetraphyllidea, Trypanorhyncha, and Lecanicephalidea to increase proglottid production. The dynamics of transmission for cestodes of humans and domestic animals require a different perspective than those of wild hosts. All strategies are reviewed within the framework of certain cestode morphological and ecological constraints. A total of 11 figures and 48 references complements the text.

Animals↗
PubMed2004

Widespread vertical transmission and associated host sex-ratio distortion within the eukaryotic phylum Microspora.

Vertical transmission (VT) and associated manipulation of host reproduction are widely reported among prokaryotic endosymbionts. Here, we present evidence for widespread use of VT and associated sex-ratio distortion in a eukaryotic phylum. The Microspora are an unusual and diverse group of eukaryotic parasites that infect all animal phyla. Following our initial description of a microsporidian that feminizes its crustacean host, we survey the diversity and distribution of VT within the Microspora. We find that vertically transmitted microsporidia are ubiquitous in the amphipod hosts sampled and that they are also diverse, with 11 species of microsporidia detected within 16 host species. We found that infections were more common in females than males, suggesting that host sex-ratio distortion occurs in five out of eight parasite species tested. Phylogenetic reconstruction demonstrates that VT occurs in all major lineages of the phylum Microspora and that sex-ratio distorters are found on multiple branches of the phylogenetic tree. We propose that VT is either an ancestral trait or evolves with peculiar frequency in this phylum. If the association observed here between VT and host sex-ratio distortion holds true across other host taxa, these eukaryotic parasites may join the bacterial endosymbionts in their importance as sex-ratio distorters.

Amphipoda↗