Fas/CD95-mediated apoptosis of type II cells is blocked by Toxoplasma gondii primarily via interference with the mitochondrial amplification loop.

Infection and Immunity
Diana HippeCarsten G K Lüder

Abstract

The intracellular protozoan Toxoplasma gondii induces persistent infections in various hosts and is an important opportunistic pathogen of humans with immature or deficient immune responses. The ability to survive intracellularly largely depends on the blocking of different proapoptotic signaling cascades of its host cell. Fas/CD95 triggers an apoptotic cascade that is crucial for immunity and the outcome of infectious diseases. We have determined the mechanism by which T. gondii counteracts death receptor-mediated cell death in type II cells that transduce Fas/CD95 ligation via caspase 8-mediated activation of the mitochondrial amplification loop. The results showed that infection with T. gondii significantly reduced Fas/CD95-triggered apoptosis in HeLa cells by inhibiting the activities of initiator caspases 8 and 9 and effector caspase 3/7. Parasitic infection dose dependently diminished cleavage of caspase 8, the BH3-only protein Bid, and the downstream caspases 9 and 3. Importantly, interference with Fas/CD95-triggered caspase 8 and caspase 3/7 activities after parasitic infection was largely dependent on the presence of caspase 9. Within the mitochondrial amplification loop, T. gondii significantly inhibited the Fas/CD95-...Continue Reading

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Citations

May 11, 2013·Apoptosis : an International Journal on Programmed Cell Death·Weijie GaoTongsheng Chen
Jan 17, 2009·Cell Division·Adam J Hume, Robert F Kalejta
Jul 25, 2009·International Journal for Parasitology·Jon P Boyle, Jay R Radke
Feb 19, 2011·International Journal for Parasitology·Tatsuya YamadaAmos Orlofsky
Jan 23, 2014·Parasitology International·Deyong ChuFumie Aosai
Nov 13, 2008·International Journal for Parasitology·Carsten G K LüderVolker T Heussler
May 22, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael P LeesNicholas C Smith
May 14, 2019·Frontiers in Microbiology·Wanbo ZhuLi Yu
May 2, 2019·Frontiers in Cellular and Infection Microbiology·Tatiane S Lima, Melissa B Lodoen
Sep 29, 2017·Frontiers in Immunology·Thaís Rigueti BrasilAndrea Cristina Vetö Arnholdt

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