Toxoplasma gondii exposes phosphatidylserine inducing a TGF- beta sub(1) autocrine effect orchestrating macrophage evasion

Toxoplasmosis is a worldwide disease caused by Toxoplasma gondii. Activated macrophages control T. gondii growth by nitric oxide (NO) production. However, T. gondii active invasion inhibits NO production, allowing parasite persistence. Here we show that the mechanism used by T. gondii to inhibit NO...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2004-11, Vol.324 (2), p.744-752
Main Authors: Seabra, SH, de Souza, W, DaMatta, R A
Format: Article
Language:English
Subjects:
Leishmania amazonensis
Toxoplasma gondii
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Summary:Toxoplasmosis is a worldwide disease caused by Toxoplasma gondii. Activated macrophages control T. gondii growth by nitric oxide (NO) production. However, T. gondii active invasion inhibits NO production, allowing parasite persistence. Here we show that the mechanism used by T. gondii to inhibit NO production persisting in activated macrophages depends on phosphatidylserine (PS) exposure. Masking PS with annexin-V on parasites or activated macrophages abolished NO production inhibition and parasite persistence. NO production inhibition depended on a transforming growth factor- beta sub(1) (TGF- beta sub(1)) autocrine effect confirmed by the expression of Smad 2 and 3 in infected macrophages. TGF- beta sub(1) led to inducible nitric oxide synthase (iNOS) degradation, actin filament (F-actin) depolymerization, and lack of nuclear factor- Kappa B (NF- Kappa B) in the nucleus. All these features were reverted by TGF- beta sub(1) neutralizing antibody treatment. Thus, T. gondii mimics the evasion mechanism used by Leishmania amazonensis and also the anti-inflammatory response evoked by apoptotic cells.
ISSN:0006-291X
DOI:10.1016/j.bbrc.2004.09.114