Paracoccidioidomycosis presents a variety of clinical manifestations
and Paracoccidioides brasiliensis can reach many tissues, most
importantly the lungs. The ability of the pathogen to interact with
host surface structures is essential to its virulence. The interaction
between P. brasiliensis and epithelial cells has been studied, with
particular emphasis on the induction of apoptosis. To investigate the
expression of different apoptosis-inducing pathways in human A549
cells, we infected these cells with P. brasiliensis Pb18SP
(subcultured) and 18R (recently isolated from cell culture and showing
a high adhesion pattern) samples in vitro. The expressions of Bcl-2,
Bak and caspase 3 were analysed by flow cytometry and DNA fragmentation
using the TUNEL technique. Apoptosis of human A549 cells was induced by
P. brasiliensis in a sample and time-dependent manner. Using an in
vitro model, our data demonstrates that caspase 3, Bak, Bcl-2 and DNA
fragmentation mediate P. brasiliensis-induced apoptosis in A549 cells.
The overall mechanism is a complex process, which may involve several
signal transduction pathways. These findings could partially explain
the efficient behaviour of this fungus in promoting tissue infection
and/or blood dissemination