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

To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella enterica serovar Typhimurium aroA was exploited as a DNA delivery system for cruzipain (SCz). In a murine model we compared SCz alone (GI) or coadministered with Salmonella carrying a plasmid encoding granulocyte-macrophage colony-stimulating factor (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) admixed with either CpG-ODN (GIII) or MALP-2, a synthetic derivative of a macrophage-activating lipopeptide of 2 kDa from Mycoplasma fermentans (GIV). The results showed that protocols that included four oral doses of SCz (GI) elicited mainly a mucosal response characterized by immunoglobulin A (IgA) secretion and proliferation of gut-associated lymphoid tissue cells, with weak systemic responses. In contrast, the protocol that included a boost with rCz plus CpG (GIII) triggered stronger systemic responses in terms of Cz-specific serum IgG titers, splenocyte proliferation, gamma interferon (IFN-gamma) secretion, and delayed-type hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significantly lower levels of parasitemia compared to controls. Protection was abolished by depletion of either CD4+ or CD8+ T cells. Parasite control was also evident from the reduction of tissue damage, as revealed by histopathologic studies and serum levels of enzymes that are markers of muscle injury in chronic Chagas' disease (i.e., creatine kinase, aspartate aminotransferase, and lactate dehydrogenase). Enhanced release of IFN-gamma and interleukin-2 was observed in GI and GII upon restimulation of splenocytes in the nonparasitic phase of infection. Our results indicate that Salmonella-mediated delivery of Cz-DNA by itself promotes the elicitation of an immune response that controls T. cruzi infection, thereby reducing parasite loads and subsequent damage to muscle tissues.
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PMID:Oral vaccination with Salmonella enterica as a cruzipain-DNA delivery system confers protective immunity against Trypanosoma cruzi. 1796 57

In natural infection, the survival of Trypanosoma cruzi, despite the complex immune response elicited including several humoral and cellular components of innate and acquired immunity, suggests that the immune system's natural responses are inherently inadequate. Consequently, it is of paramount importance to find alternatives to direct the immune system before infection, and redirect it after infection, to obtain a prophylactic and therapeutic vaccine. Herein, we review the recent advances in vaccine research and the development of the major antigen candidates, including cruzipain, trans-sialidase, amastigote surface protein, paraflagellar rod protein, among others. In the last 5 years, experimental works have been conducted to analyze DNA delivery systems, including viruses and bacteria, as well as immunomodulators such as CpG-oligodeoxynucleotide, macrophage-activating lipopeptide from Mycoplasma fermentans, glycolipid alpha-galactosylceramide, granulocyte-macrophage colony-stimulating factor, IL-12 and other cytokines and chemokines. The review also covers articles that shed light on some mechanisms of innate and adaptive immunity against T. cruzi, which improved our knowledge and provided potentially useful tools to fight infection. A better understanding of the protective immune responses that can effectively arrest T. cruzi survival in the mammalian host is critical for the development of vaccines against Chagas disease.
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PMID:Vaccination approaches against Trypanosoma cruzi infection. 1953 17