Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. The micronemal protein MIC3, which is a potent adhesin of T. gondii, could be a significant candidate vaccine against toxoplasmosis. In this study, all CBA/J mice intramuscularly vaccinated with a plasmid encoding the immature form of the MIC3 protein (pMIC3i) produced specific anti-MIC3 immunoglobulin G (IgG) antibodies, and their sera displayed high antibody titers. This response was increased by the coadministration of a plasmid encoding the granulocyte-macrophage colony-stimulating factor (pGM-CSF). Similarly, a specific and significant cellular immune response was obtained in mice immunized with pMIC3i, and this response was markedly enhanced by pGM-CSF coadministration. The cellular immune response was associated with the production of gamma interferon IFN-gamma and interleukin-2 (IL-2), indicating that this was a Th1-type response. This was confirmed by the production of large amounts of IgG2a. Mice immunized with pMIC3i displayed significant protection against an oral challenge with T. gondii 76K cysts, exhibiting fewer brain cysts than did the control mice. Coadministration of pGM-CSF enhanced this protection. In conclusion, this study describes the design of a potent DNA vaccine encoding the novel T. gondii target antigen, MIC3 protein, that elicits a strong specific immune response as well as providing effective protection against T. gondii infection. In the attempt to achieve complete protection against toxoplasmosis, MIC3 is a good candidate vaccine which could be combined with other relevant and previously described candidates, such as SAG1 and GRA4.
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PMID:The MIC3 gene of Toxoplasma gondii is a novel potent vaccine candidate against toxoplasmosis. 1457 40

To develop a multiantigenic vaccine against toxoplasmosis, two Toxoplasma gondii antigens, SAG1 and GRA4 selected on the basis of previous immunological and immunization studies, were chosen. We showed that DNA-based immunization with plasmids expressing GRA4 (pGRA4) or SAG1 (pSAG1mut) reduced mortality of susceptible C57BL/6 mice upon oral challenge with cysts of the 76K type II strain (62% survival). Immunization with pGRA4 and pSAG1mut, enhanced the protection (75% survival). This protection was further increased by co-inoculation with a plasmid encoding the granulocyte-macrophage colony-stimulating factor (GM-CSF) (87% survival). This latter DNA cocktail provided significant protection of less susceptible outbred Swiss OF1 mice against the development of cerebral cysts. A significantly higher survival of newborns from immunized outbred mice exposed to infection during gestation was observed (4.25+/-3.77 live pups/litter) in comparison to non-immunized mice (1.08+/-2.15 live pups/litter) without preventing parasite vertical transmission. Analysis of the immune response showed that protected animals developed a specific humoral and cellular Th1 response to native T. gondii SAG1 and GRA4 antigens. Our data demonstrated that protection was improved by associating antigens (SAG1 and GRA4) and cytokine (GM-CSF) for further development of a multiantigenic vaccine against toxoplasmosis.
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PMID:Evaluation of protective effect of DNA vaccination with genes encoding antigens GRA4 and SAG1 associated with GM-CSF plasmid, against acute, chronical and congenital toxoplasmosis in mice. 1593 21

The present study was conducted mainly to evaluate the contribution of the cellular and the humoral responses in protection conferred by the MIC3 DNA vaccine (pMIC3i) that was proved as a potent vaccine against toxoplasmosis. We performed the adoptive transfer of CD4(+) and CD8(+) T lymphocytes from pMIC3i immunized mice to naive ones and the role of humoral immunity was evaluated by in vitro invasion assays. We also constructed plasmids encoding the EGF-like domains and the Lectin-like domain of MIC3, to define which domains of MIC3 are involved in the protection. Furthermore, the adjuvant effect of the GM-CSF-expressing vector (granulocyte-macrophage colony-stimulating factor) required the precise temporal and spatial codelivery of GM-CSF with antigen, thus, we constructed a bicistronic plasmid expressing MIC3 and GM-CSF. In conclusion, the protection induced by pMIC3i was mainly mediated by CD4(+) and CD8(+) T lymphocytes and both EGF and Lectin domains of MIC3 conferred protection. Furthermore, the codelivery of GM-CSF by a bicistronic plasmid appeared to be a most effective way for enhancing the adjuvant properties of GM-CSF.
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PMID:Further analysis of protection induced by the MIC3 DNA vaccine against T. gondii: CD4 and CD8 T cells are the major effectors of the MIC3 DNA vaccine-induced protection, both Lectin-like and EGF-like domains of MIC3 conferred protection. 1942 7