Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An oral administration of partially purified LPSw, a lipopolysaccharide (LPS) from wheat flour, at a concentration of 20 ng/ml in drinking water beginning 1d after infection significantly decreased mouse mortality and prevented animal weight loss in acute infection with Toxoplasma gondii. Whereas 71% (5/7) of mice in a control group that did not receive LPSw died of toxoplasmosis, only 14% (1/7) of mice treated with LPSw died (p less than 0.05). The administration of LPS purified from Bordetella pertussis also significantly decreased the mortality of infected mice. LPS from Escherichia coli and synthetic lipid A (LA-15-PP(506)), however, did not show a significant decrease in mortality.
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PMID:Homeostasis as regulated by activated macrophage. VI. Protective effect of LPSw (a lipopolysaccharide from wheat flour) against acute infection by Toxoplasma gondii in mice. 139 45

The role of recombinant murine beta interferon (rMuIFN-beta) and recombinant human IFN-beta (rHuIFN-beta) in resistance to Toxoplasma gondii was examined. rMuIFN-beta protected mice against a lethal infection with the parasite. The protective effect appeared to depend on the concomitant release of gamma interferon. rMuIFN-beta did not activate murine peritoneal macrophages to inhibit or kill T. gondii whether used alone or in combination with lipopolysaccharide (LPS). rHuIFN-beta did not activate human monocyte-derived macrophages to inhibit or kill T. gondii when 5-day-old monocyte-derived macrophages were used. In contrast, significant killing of T. gondii was noted when 10-day-old monocyte-derived macrophages were used. The addition of LPS enhanced this effect. These results revealed a role for IFN-beta in the mechanisms of defense against T. gondii and suggest its potential use in the treatment of toxoplasmosis in humans.
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PMID:Role of beta interferon in resistance to Toxoplasma gondii infection. 190 31

This study was designed to explore the effects of acute nutritional deprivation (starvation) on macrophage function in mice. In vivo macrophage activity was increased by starvation, as determined by multiplication of Listeria monocytogenes in both spleens and livers after intravenous injection. Similarly, in vitro studies revealed that the capacity of peritoneal macrophages to kill listeria was enhanced by starvation. This function was increased further by the addition of small concentrations of lipopolysaccharide (LPS; 10-100 ng/ml). The bactericidal activity of macrophages from starved mice, however, did not reach the levels observed with macrophages from BCG-infected mice. Furthermore, LPS did not appear to be an important second signal for macrophage activation in vivo, as LPS-unresponsive mice (C3H/HeJ and A/J) were protected by starvation. In contrast to these results we found that starved mice were not protected against Toxoplasma gondii infection and that macrophages from starved mice were unable to prevent multiplication of toxoplasma trophozoites in vitro. In toto, these experiments suggest that macrophage function is enhanced by starvation, but that this enhancement is not sufficient to fulfill all criteria for macrophage activation.
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PMID:Effect of acute nutritional deprivation on immune function in mice. I. Macrophages. 640 45

To investigate the role of astroglia in intracerebral immune response to Toxoplasma gondii, astrocytes cultured from mouse brain were inoculated with mouse-virulent or -avirulent toxoplasma strains. In comparison to microglia/ brain macrophages, astrocytes as host cells allowed stronger proliferation of avirulent parasites. Toxoplasma infection of astroglia was accompanied by release of interleukin- (IL)1 alpha, IL-6, and granulocyte/macrophage colony-stimulating factor (GM-CSF) activity, whereas alternative challenge by lipopolysaccharide (LPS) evoked no IL-1 response and significantly higher titers of IL-6 and GM-CSF. At the mRNA level, both stimuli induced transcription of all three cytokines in astrocytes. Secretion of IL-1 and IL-6 upon infection was triggered by T. gondii brady- and tachyzoites in a time- and dose-dependent manner. Heat killing of parasites, but not an exposure to polymyxin B, abrogated their cytokine-inducing activity, thus indicating that an LPS-independent stimulus is provided by T. gondii. When administered in combination, LPS synergistically augmented the IL-1-inducing effect of toxoplasma infection. In comparison, T. gondii-induced, but not an LPS-triggered, IL-6 response of astrocytes resisted to antagonization with IL-10. The IL-6 response of parasitized astroglia was up-regulated by external tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta 1, with only TNF-alpha enhancing simultaneous release of IL-1. Substantial secretion of IL-10 and TNF-alpha was detected in T. gondii-infected microglia, but not in astrocyte cultures. A possibly autocrine stimulation of infected astroglia via IL-1 was found to be unlikely, since addition of IL-1 receptor antagonist did not affect the release of IL-6 and GM-CSF while inhibiting these responses in IL-1-treated cells. The findings substantiate a separate, T. gondii-induced pathway of astroglia activation characterized by the release of IL-1 which may drive local inflammatory reaction both at initial infection of the brain and during reactivating toxoplasmosis.
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PMID:Cytokine responses induced by Toxoplasma gondii in astrocytes and microglial cells. 920 8

Injection of 10 cysts of Toxoplasma gondii (Me49 strain) into Swiss Webster mice results in 1) an acute phase of infection lasting for 2-3 wk, characterized by weight loss, and 2) a chronic phase in which surviving mice show either partial weight recovery (Gainers) or persistent, although stable, cachexia (Nongainers). In response to a second immunological stimulation with lipopolysaccharide (LPS) in the chronic phase of the infection, it is shown that 1) the increase in energy expenditure was more prolonged in both groups of infected mice than in controls, 2) the intensity and duration of hypophagia were also differently affected with Nongainers > Gainers > controls, and 3) the infected mice had higher serum levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-10 and a lower ratio of IL-10 to TNF-alpha than controls. In contrast, serum IL-4 increased to the same level in all three groups. Evaluation of the permeability of the blood-brain barrier by intravenous injection of Evans blue revealed a marked staining in the brain of only the infected Nongainers. Taken together, these results indicate that, in mice with chronic toxoplasmosis, a second nonspecific challenge (with LPS) exacerbates the hypophagic and hypermetabolic states, the latter being associated with hyperresponsiveness in TNF-alpha and IL-10 production. Furthermore, the greater exacerbation of the hypophagic state in mice showing persistent cachexia may be due to a preexisting higher permeability of the blood-brain barrier, which would allow a greater access of plasma-borne cytokines and/or other neuroimmunologically active substances to the central nervous system.
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PMID:Metabolic-cytokine responses to a second immunological challenge with LPS in mice with T. gondii infection. 953 Jan 26

Dendritic cells (DC) are potent antigen-presenting cells that can stimulate T cell responses by secreting cytokines. During Toxoplasma gondii infection, host immunity is mediated by interferon-gamma, which is induced by interleukin-12 (IL-12). Whether T. gondii infection would stimulate human DC to produce IL-12 was determined. DC were generated from human peripheral blood mononuclear cells cultured with recombinant human granulocyte-macrophage colony-stimulating factor and recombinant human IL-4. DC secreted high levels of IL-12 in response to lipopolysaccharide but not to either live T. gondii tachyzoites or soluble antigen. However, IL-12 production in response to T. gondii was observed when DC were cocultured in contact with lymphocytes isolated from seropositive donors. Ligation of CD40:CD154 was partially essential for IL-12 secretion. These data demonstrate that signals obtained from contact with sensitized lymphocytes are critical for human DC to secrete IL-12 in response to T. gondii.
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PMID:Sensitized lymphocytes and CD40 ligation augment interleukin-12 production by human dendritic cells in response to Toxoplasma gondii. 987 33

Cell mediated immunity is very important for host defence against intracellular pathogens and many studies have shown the role of the production of nitric oxide (NO) by interferon (IFN)-gamma/lipopolysaccharide (LPS)-activated macrophages. As the progesterone level increases during pregnancy in mammals, and as previous studies have shown that progesterone inhibits inducible nitric oxide synthase (iNOS) expression and NO production, we aimed to investigate whether progesterone might modulate intracellular replication of Toxoplasma gondii in macrophages. Our results showed that progesterone does not influence T. gondii replication in non-activated RAW 264.7 cells, and although progesterone inhibits NO production induced by IFN-gamma/LPS, we observed that it fails to restore the growth of T. gondii blocked by IFN-gamma/LPS. After discussing the reasons for this apparent discrepancy, we concluded that progesterone has no direct effect on the macrophage response. The real effect of the sex steroids in T. gondii infection and their implication in clinical toxoplasmosis therefore need to be investigated further to involve wider mechanisms of the immune system.
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PMID:Progesterone fails to modulate Toxoplasma gondii replication in the RAW 264.7 murine macrophage cell line. 1201 Apr 82

Production of nitric oxide by activated murine macrophages is thought to represent an important mechanism to restrict replication of the obligate intracellular parasite Toxoplasma gondii. In this study, we characterised the effect of T. gondii on nitric oxide production and expression of the inducible nitric oxide synthase and determined the functional significance of a parasite-induced evasion of this potential effector mechanism. Infection of primary bone marrow-derived macrophages or monocytic/macrophage RAW264.7 cells with a mouse-avirulent T. gondii strain significantly decreased nitric oxide production that had been induced by activation with either interferon-gamma or lipopolysaccharide or interferon-gamma plus lipopolysaccharide. Importantly, down-regulation of nitric oxide production by T. gondii enabled considerable parasite replication in macrophages activated with interferon-gamma alone or lipopolysaccharide alone. Furthermore, supplementation of endogenous nitric oxide by addition of sodium nitroprusside to levels as observed in uninfected interferon-gamma- or lipopolysaccharide-activated macrophages almost completely abrogated replication of T. gondii. Although T. gondii also partially inhibited the vigorous nitric oxide production induced by interferon-gamma along with lipopolysaccharide, the magnitude of inhibition did not suffice to allow intracellular propagation of the parasite in these synergistically activated macrophages. Inhibition of interferon-gamma-, lipopolysaccharide- and interferon-gamma plus lipopolysaccharide-induced nitric oxide production coincided with reduced inducible nitric oxide synthase protein levels. Such down-regulation required the presence of intracellular parasites as determined by immunofluorescence microscopy. Inducible nitric oxide synthase transcripts induced by interferon-gamma alone or in combination with lipopolysaccharide were also dose-dependently down-regulated after infection of RAW264.7 cells with T. gondii. In conclusion, this evasion strategy enables parasite replication in macrophages moderately activated by interferon-gamma or lipopolysaccharide, but does not suffice to evade the anti-parasitic activity of macrophages fully activated by interferon-gamma plus lipopolysaccharide. Nitric oxide production and its partial inhibition by the parasite may modulate the parasite-host equilibrium during toxoplasmosis.
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PMID:Reduced expression of the inducible nitric oxide synthase after infection with Toxoplasma gondii facilitates parasite replication in activated murine macrophages. 1286 83

Cytotoxic-activated macrophages control Toxoplasma gondii growth by producing nitric oxide (NO). However, the parasite can partially inhibit NO production. NO is generated from arginine within the polyamine biosynthetic pathway. Two enzymes of this pathway are ornithine, decarboxylase (ODC) and arginine decarboxylase (ADC). The aim of the present work was to investigate whether T. gondii is able to modulate polyamine metabolism in macrophages. Toxoplasma gondii infection did not affect basal ODC or ADC activity. However, lipopolysaccharide induced an increase in ODC activity. Polyamine-treated macrophages exhibited a T. gondii-infection index similar to controls but a higher adhesion index; the parasite did not grow in methyl-ornithine (ODC inhibitor)-treated macrophages. The parasites were able to take up putrescine with a Km of 0.92 microM, indicating the presence of a high-affinity putrescine-transporter system. Putrescine-treated T. gondii actively penetrated macrophages and Vero cells. However, NO production and lysosomal parasitophorous vacuole fusion were not inhibited. Considered together, these results demonstrate that T. gondii requires polyamines for multiplication. However, as opposed to Trypanosoma cruzi and because of a relatively high-affinity putrescine-transporter system in the parasite, constitutive macrophage levels of putrescine seem sufficient to support T. gondii survival and multiplication.
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PMID:Endogenous polyamine levels in macrophages is sufficient to support growth of Toxoplasma gondii. 1527 85

Mammalian Toll-like receptors (TLRs) recognize microbial pathogen-associated molecular patterns and are critical for innate immunity against microbial infection. Diacylglycerol (DAG) kinases (DGKs) regulate the intracellular levels of two important second messengers involved in signaling from many surface receptors by converting DAG to phosphatidic acid (PA). We demonstrate that the zeta isoform of the DGK family (DGKzeta) is expressed in macrophages (Mphi) and dendritic cells. DGKzeta deficiency results in impaired interleukin (IL) 12 and tumor necrosis factor alpha production following TLR stimulation in vitro and in vivo, increased resistance to endotoxin shock, and enhanced susceptibility to Toxoplasma gondii infection. We further show that DGKzeta negatively controls the phosphatidylinositol 3-kinase (PI3K)-Akt pathway and that inhibition of PI3K activity or treatment with PA can restore lipopolysaccharide-induced IL-12 production by DGKzeta-deficient Mphi. Collectively, our data provide the first genetic evidence that an enzyme involved in DAG/PA metabolism plays an important role in innate immunity and indicate that DGKzeta promotes TLR responses via a pathway involving inhibition of PI3K.
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PMID:Diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii. 1737 30


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