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ABSTRACT: Monocyte/macrophages represent the first line of defense against protozoan parasites. Different mechanisms of monocyte suppression
by Toxoplasma gondii that sustain parasite invasion and persistence have been described, including apoptosis. In the present study, we investigated
the effect of microbial excretory–secretory polypeptides, namely the microneme protein MIC3 and the dense granule antigen
GRA1, on apoptosis of monocytes from patients with congenital toxoplasmosis and healthy individuals. We found that GRA1 but
not MIC3 could induce apoptosis of monocytes, observing the effect in samples from both Toxoplasma-infected and uninfected individuals, thus ruling out involvement of mechanisms of apoptosis linked to adaptive immunity or
a cellular context related to infection. Selective inhibition of TGF-β type I receptors reversed GRA1-induced apoptosis, indicating
that this apoptosis involved canonical TGF-β signaling. By using TGF-β-neutralizing antibodies, we showed that monocyte apoptosis
required endogenous TGF-β and that GRA1 stimulation activated TGF-β transcription and expression in monocytes but not lymphocytes,
suggesting involvement of an autocrine TGF-β-mediated mechanism in GRA1-induced apoptosis.
Keywords
Toxoplasma gondii
–GRA1–Apoptosis–Monocytes–TGF-β
APOPTOSIS 04/2012; 16(6):551-562. · 4.79 Impact Factor
