The intracellular cycle of Trypanosoma cruzi in mammalian
host cells involves the differentiation of dividing amastigote
forms into flagellated trypomastigote forms. The mechanism(s) regulating
the growth and differentiation of the intracellular parasites is (are)
not known. The number of parasites in infected cells can be several hundred
and may be enough
to induce apoptosis, a suicide-like death programme, generating products
(e.g. nuclear proteins) that could function as
signals to initiate the differentiation of amastigotes into trypomastigotes.
Murine fibroblasts infected with T. cruzi were
examined during a 5-day course of infection for evidence of apoptosis.
However, characteristics of apoptosis, including
degeneration of nuclear structure, condensation of chromatin, loss of plasma
membrane integrity, or the cleavage of DNA
into nucleosomal fragments, were not observed. Therefore, it is unlikely
that products resulting from host cell apoptosis
function to induce parasite differentiation. The possibility that T.
cruzi might inhibit host cell apoptosis by increasing
intracellular levels of Bcl-2, an endogenous inhibitor of apoptosis, was
then investigated. Analysis of infected cells by flow
cytometry did not demonstrate a significant amount of intracellular Bcl-2.
This suggests that if the parasite is inhibiting
host cell apoptosis, it is by a method that does not involve increasing
levels of Bcl-2.
P100W4-2 Analysis of host cell apoptosis in vitro and in vivo by Trypanosoma cruzi infection
