Affiliation:
1. Division of Infectious Diseases, Department of Medicine,1
2. Department of Microbiology and Immunology,2 and
3. Department of Pathology,3 Albert Einstein College of Medicine, Bronx, New York 10461
Abstract
ABSTRACT
The ability of
Toxoplasma gondii
tachyzoites to differentiate into latent bradyzoite forms is essential for pathogenesis of clinical disease. We examined the effects of cyclic nucleotides on
T. gondii
bradyzoite differentiation in vitro. Differentiation of tachyzoites to bradyzoites was measured in an immunofluorescence assay using ME49 or its clonal derivative PLK, two well-characterized
T. gondii
strains. Treatment of human fibroblast cultures infected with
T. gondii
with 8-(4-chlorophenylthio)-cyclic GMP (CPT-cGMP), a membrane-permeable, nonhydrolyzable analogue of cGMP, resulted in an increased percentage of bradyzoite-positive vacuoles. Cyclic AMP (cAMP) also induced in vitro conversion of PLK, but the method of cAMP elevation was critical. Forskolin raises cAMP levels transiently and induced bradyzoites, whereas agents predicted to cause sustained elevation of cAMP were inhibitory to parasite conversion. Levels of cAMP were measured in host cells and extracellular tachyzoites. Forskolin, CPT-cGMP, and agents known to induce bradyzoite formation elevated cAMP in host cells and PLK parasites. These data suggest cyclic nucleotide signaling pathways are important in the stress-induced conversion of
T. gondii
tachyzoites to bradyzoites. Furthermore, because cAMP elevation was seen in PLK but not RH, a
T. gondii
strain that did not differentiate well in our assay, cAMP signaling within the parasite is likely to be critical.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
63 articles.
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