Toxoplasma Gondii Triggers Gi-dependent Pi 3-kinase Signaling Required for Inhibition of Host Cell Apoptosis.
From: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401, USA.
Journal of cell science
- Publish Date: May 2006
- ISSN: 0021-9533
- Volume: 119
- Issue: Pt 10
- Pages: 2119-26
- Medium: Print
- Language: English
- Citation (JAMA): Kim Leesun, Denkers Eric Y, et al. Toxoplasma Gondii Triggers Gi-dependent Pi 3-kinase Signaling Required for Inhibition of Host Cell Apoptosis.. J. Cell. Sci. May 2006;119:2119-26
Abstract
Infection with the intracellular parasite Toxoplasma gondii renders cells resistant to multiple pro-apoptotic signals, but underlying mechanisms have not been delineated. The phosphoinositide 3-kinase (PI 3-kinase) pathway and the immediate downstream effector protein kinase B (PKB/Akt) play important roles in cell survival and apoptosis inhibition. Here, we show that Toxoplasma infection of mouse macrophages activates PKB/Akt in vivo and in vitro. In a mixed population of infected and non-infected macrophages, activation is only observed in parasite-infected cells. The PI 3-kinase inhibitors wortmannin and LY294002 block parasite-induced PKB phosphorylation. PKB activation occurs independently of Toll-like receptor adaptor protein MyD88 but uncoupling of Gi-protein-mediated signaling with pertussis toxin prevents PKB phosphorylation. Moreover, in the presence of PI 3-kinase inhibitors or pertussis toxin, not only PKB activation but also ERK1/2 activation during T. gondii infection is defective. Most importantly, the parasite’s ability to induce macrophage resistance to pro-apoptotic signaling is prevented by incubation with PI 3-kinase inhibitors. This study demonstrates that T. gondii exploits host Gi-protein-dependent PI 3-kinase signaling to prevent induction of apoptosis in infected macrophages.
Mesh Headings (Keywords): 1-Phosphatidylinositol 3-Kinase, Animals, Apoptosis, Flow Cytometry, GTP-Binding Protein alpha Subunits, Gi-Go, In Situ Nick-End Labeling, Lipopolysaccharides, Macrophages, Mice, Mice, Inbred C57BL, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Proto-Oncogene Proteins c-akt, Signal Transduction, Toxoplasma, Toxoplasmosis
Check for Full Text / PubMed Unique Identifier (PMID): 16638808
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