Dendritic cells : a double-edged sword in immune responses during chagas disease

Dendritic cells (DCs) are the most important member of the antigen presenting cells group due to their ability to recognize antigen at the infection site and their high specialized antigen internalization capacity. These cells have central role in connecting the innate and adaptive immune responses against Trypanosoma cruzi, the causative agent of Chagas disease. These first line defense cells modulate host immune response depending on type, maturation level, cytokine milieu and DC receptor involved in the interactions with T. cruzi, influencing the development of the disease clinic forms. Here, we present a review of DCs–T. cruzi interactions both in human and murine models, pointing out the parasite ability to manipulate DCs activity for the purpose of evading innate immune response and assuring its own survival and persistence

Kinetic studies on parasitophorous vacuole formation and escape by the two infective forms of Trypansoma cruzi in mammalian cells

Estudamos neste trabalho alguns aspectos da invasao celular por formas tripomastigotas metaciclicas e amastigotas extracelulares do Trypanosoma cruzi (cepa G). A primeira parte do trabalho sugere que a cinetica de formacao e escape do vacuolo parasitoforo em celulas HeLa e Vero apresentam diferencas de acordo com a forma do parasita estudada. A mobilizacao de lisossomos com elevacao do pH intracelular afetou tanto a invasao quanto o escape do vacuolo parasitoforo das formas tripomastigotas metaciclicas mas nao influendiou a cinetica de escape das formas amastigotas. extracelulares. Celulas mutantes em acido sialico foram utilizadas como alvo e observamos que a defiCiência desta molecula facilitou o escape das duas formas do vacuolo parasitoforo, porem teve consequencias distintas na invasao pelas duas formas. Ensaios hemoliticos foram realizados e observamos atividade da hemolisina (Tc-TOX) apenas nas formas amastigotas e as formas tripomastigotas nao permanecem viaveis apos 12 horas de ensaio. A invasao de formas tripomastigotas metaciclicas e amastigotas extracelulares em celulas HeLa e Vero foi afetada de forma diferente quando utilizamos inibidores de sinalizacao de calcio. Esses resultados sugerem que tripomastigotas metaciclicos e amastigotas extracelulares utilizam mecanismos com caracteristicas particulares para invadir a celula hOSDedeira e escanar dos vacuolos parasitoforosBV UNIFESP: Teses e dissertaçõe

Parameters Affecting Cellular Invasion and Escape from the Parasitophorous Vacuole by Different Infective Forms of Trypanosoma cruzi

In this study we have examined certain aspects of the process of cell invasion and parasitophorous vacuole escape by metacyclic trypomastigotes and extracellular amastigote forms of Trypanosoma cruzi   (G strain). Using Vero (and HeLa) cells as targets, we detected differences in the kinetics of vacuole escape by the two forms. Alcalinization of intercellular pH influenced both invasion as well as the escape from the parasitophorous vacuole by metacyclic trypomastigotes, but not the escape kinetics of extracellular amastigotes. We used sialic acid mutants as target cells and observed that the deficiency of this molecule facilitated the escape of both infective forms. Hemolysin activity was only detected in extracellular amastigotes and neither form presented detectable transialidase activity. Invasion of extracellular amastigotes and trypomastigotes in Vero cells was affected in different ways by drugs that interfere with host cell Ca2+ mobilization. These results are in line with previous results that indicate that metacyclic trypomastigotes and extracellular amastigote forms utilize mechanisms with particular features to invade host cells and to escape from their parasitophorous vacuoles

In vitro phenotypic screening of 7-chloro-4-amino(oxy)quinoline derivatives as putative anti-Trypanosoma cruzi agents

In this study, a series of 22 pre-synthesized 7-chloro-4-mino(oxy)quinoline derivatives was assayed in vitro as potential antichagasic agents. A primary screening against Trypanosoma cruzi epimastigotes and a non-specific cytotoxicity assay on murine fibroblasts were simultaneously performed, resulting quinolines 3, 7 and 12 with great selectivity (SI) on the extracellular parasite (SI7, SI3 , SI12 and SIBZ >9.44). Therefore, the activity of these derivatives was evaluated on intracellular amastigotes, achieving derivative 7 the best SI (SI = 12.73). These results, supported by the in silico prediction of a good oral bioavailability and a suitable risk profile, propose the 4-amino-7-chloroquinoline scaffold as a potential template for designing trypanocidal prototypes.Departamento Administrativo de Ciencia, Tecnología e Innovación [CO] Colciencias5507-543-31904Programa: Bioprospección y desarrollo de ingredientes naturales para las industrias cosmética, farmacéutica y de productos de aseo con base en la biodiversidad colombianan