TRYPANOSOMA CRUZI MECHANISMS OF IMMUNE RESISTANCE

  • Tanowitz, Herbert B., (PI)

Project: Research project

Description

In previous studies from out laboratory we have detailed the effect of
Trypanosoma cruzi infection on the generation of intracellular second
messengers such as cAMP and calcium. The mechanism of these effects
seems to be at the level of the guanine nucleotide binding proteins. We
have also described the effect of verapamil on the course of murine
Chagas' disease, again implicating calcium as an important factor in the
pathogenesis of the cardiomyopathy that attends this infection. We and others have made the observation that the extent of parasitism is
unrelated to the functional impairment. Consequently, this has led us
to an examination of the intracellular communication between infected
and uninfected cells. In an effort to understand this relationship we
will study coordinated communication between infected and uninfected
myoblasts and between infected and uninfected cardiocytes via gap
junctions. We will study whether T.cruzi infection results in altered
expression of gap junctions. Toward this end we will compare gap
junctions mRNA levels and immunolocalized gap junctions in infected and
uninfected myoblasts and cardiocytes. We will also study the influence
of infection on receptor-dependent and independent mobilization of
intracellular calcium in single cells. The role of phospholipdid
metabolism in this process will also be investigated. Finally, since we have already shown in a murine model that verapamil, a
calcium channel blocker ameliorates the consequences of this infection
on the heart we will determine the mode of action of this agent and
other related compounds on intracellular calcium metabolism in infected
myoblasts and cardiocytes. Alterations in intracellular calcium
metabolism and gap junction expression may explain, in part, the
contractility and electrical conduction abnormalities that attends
Chagas' disease.
StatusFinished
Effective start/end date7/1/781/31/07

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)