Heme-induced Trypanosoma cruzi proliferation is mediated by CaM kinase II.

Trypanosoma cruzi, the etiologic agent of Chagas disease, is transmitted through triatomine vectors during their blood-meal on vertebrate hosts. These hematophagous insects usually ingest approximately 10mM of heme bound to hemoglobin in a single meal. Blood forms of the parasite are transformed into epimastigotes in the crop which initiates a few hours after parasite ingestion. In a previous work, we investigated the role of heme in parasite cell proliferation and showed that the addition of heme significantly increased parasite proliferation in a dose-dependent manner [1]. To investigate whether the heme effect is mediated by protein kinase signalling pathways, parasite proliferation was evaluated in the presence of several protein kinase (PK) inhibitors. We found that only KN-93, a classical inhibitor of calcium-calmodulin-dependent kinases (CaMKs), blocked heme-induced cell proliferation. KN-92, an inactive analogue of KN-93, was not able to block this effect. A T. cruzi CaMKII homologue is most likely the main enzyme involved in this process since parasite proliferation was also blocked when Myr-AIP, an inhibitory peptide for mammalian CaMKII, was included in the cell proliferation assay. Moreover, CaMK activity increased in parasite cells with the addition of heme as shown by immunological and biochemical assays. In conclusion, the present results are the first strong indications that CaMKII is involved in the heme-induced cell signalling pathway that mediates parasite proliferation.

Microsporidia and acquired immunodeficiency syndrome

Microsporidia is a common term that has been used to refer to a group of eukaryotic, obligate intracellular protozoan parasites belonging to the phylum Microspora. They are important agricultural parasites, contaminating commercial insects; they are also important by infecting laboratory rodents, rabbits and primates. Ever since the early cases found by Magarino Torres, who reported the presence of Encephalitozoon in a patient suffering of a meningoencephalomyelitis, some human pathology caused by microsporidia has been described. However, only after the acquired immunodeficiency syndrome outbreak have these organisms appeared as significant etiological agents in different pathologies. Even so, they remain underestimated. In the present article, the importance of microsporidia for the human pathology in immunocompromised host has been stressed

Trypanosoma cruzi: histopathology and time course infection in indomethacin - treated mice

A indometacina administrada por via oral ou intraperitoneal, na dose de 5mg/kg diariamente, durante infecçäo experimental em camundongos por Trypanosoma cruzi, provocou o aparecimento de reaçöes adversas similares àquelas observadas através do emprego de outros antiinflamatórios, tais como os corticosteróides. A parasitemia observada nos camundongos pertencentes ao grupo dos tratados pela indometacina foi significativamente mais elevada que nos grupos-controle. A taxa de mortalidade correlacionou-se aos níveis de parasitemia. Foram observados em quase todos os tecidos dos camundongos pertencentes ao grupo dos tratados com indometacina e infectados pelo T. cruzi cepa Y, do que nos grupos-controle normais. Näo foi observada infiltraçäo celular em camundongos tratados pela indometacina (tecidos infectados) enquanto um infiltrado duro de células mononucleares foi observado nos grupos-controle. As implicaçöes clínicas em pacientes chagásicos säo discutidas

Trypanosoma cruzi invasion of structures related to development and central nervous system / Trypanosoma cruzi invasion of structures related to development and central nervous system

The purpose of the present study was to evaluate the importance of host immune response in the development of T. cruzi infection and the associated tissue lesions, using newborn mice as immunodeficient model. In adult mice, foci of inflammatory infiltrate were found in almost all tissues except in central nervous system, 2 weeks or more after infection. In infected newborn mice a heavy invasion of tissues by T. cruzi were observed, but inflammatory lesions were not found. Colonization of central nervous system was discret since only 3 per cent of newborn mice were positive. Parasitemia start early and reached higher levels in newborn mice than in adults and mortality began early, on the 9th day. Cartilage and bone marrow as well the glandular system, incluing the thymus, were heavier infected in newborn mice, than in adult mice. These results show that a hard tissue invasion of T. cruzi although without inflammatory lesions leads the experimental infected animals to death. These results are similar to our previous reports using athymic nude mice as a model of immunodeficiency. In the present experiment cartilage and brain were negative in adult mice.