INVESTIGADORES
CAZORLA Silvia Ines
artículos
Título:
Salmonella as cruzipain-DNA delivery system generate a protective immune response against T. cruz
Autor/es:
CAZORLA SI, BECKER PD, FRANK FM, EBENSEN T, SARTORI MJ, CORRAL R, MALCHIODI EL, GUZMÁN CA
Revista:
INFECTION AND IMMUNITY
Editorial:
American Society For Microbiology
Referencias:
Lugar: Estados Unidos; Año: 2008 p. 324 - 333
ISSN:
0019-9567
Resumen:
To stimulate both local and systemic immune responses against Trypanosoma cruzi, Salmonella
enterica serovar Typhimurium aroA was exploited as DNA delivery system for cruzipain (SCz). In a
murine model we compared SCz alone (GI) or co-administered with Salmonella carrying a plasmid
encoding GM-CSF (GII), as well as protocols in which SCz priming was followed by boosting with recombinant cruzipain (rCz) add-mixed with either CpG-ODN (GIII) or MALP-2 (GIV). The results
showed that protocols including four oral dosis of SCz (GI), elicited mainly a mucosal response characterized by IgA secretion and proliferation of GALT cells, with weak systemic responses. In contrast, the protocol including boost with rCz+CpG (GIII) triggered stronger systemic responses in
terms of Cz-specific serum IgG titers, splenocytes proliferation and INF-ã secretion, and delayed type
hypersensitivity response. Trypomastigote challenge of vaccinated mice resulted in significant lower
levels of parasitemia respect 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 which are markers of muscle injury in chronic
Chagas disease (i.e., creatine kinase, aspartate aminotransferase and lactate dehydrogenase). Enhanced
release of IFN-ã and IL-2 was observed in GI and GII upon re-stimulation of splenocytes on the non-
parasitic 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.