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Akt and SHIP Modulate Francisella Escape from the Phagosome and Induction of the Fas-Mediated Death Pathway

Francisella tularensis infects macrophages and escapes phago-lysosomal fusion to replicate within the host cytosol, resulting in host cell apoptosis. Here we show that the Fas-mediated death pathway is activated in infected cells and correlates with escape of the bacterium from the phagosome and the...

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Autores principales: Rajaram, Murugesan V. S., Butchar, Jonathan P., Parsa, Kishore V. L., Cremer, Thomas J., Amer, Amal, Schlesinger, Larry S., Tridandapani, Susheela
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775408/
https://www.ncbi.nlm.nih.gov/pubmed/19936232
http://dx.doi.org/10.1371/journal.pone.0007919
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author Rajaram, Murugesan V. S.
Butchar, Jonathan P.
Parsa, Kishore V. L.
Cremer, Thomas J.
Amer, Amal
Schlesinger, Larry S.
Tridandapani, Susheela
author_facet Rajaram, Murugesan V. S.
Butchar, Jonathan P.
Parsa, Kishore V. L.
Cremer, Thomas J.
Amer, Amal
Schlesinger, Larry S.
Tridandapani, Susheela
author_sort Rajaram, Murugesan V. S.
collection PubMed
description Francisella tularensis infects macrophages and escapes phago-lysosomal fusion to replicate within the host cytosol, resulting in host cell apoptosis. Here we show that the Fas-mediated death pathway is activated in infected cells and correlates with escape of the bacterium from the phagosome and the bacterial burden. Our studies also demonstrate that constitutive activation of Akt, or deletion of SHIP, promotes phago-lysosomal fusion and limits bacterial burden in the host cytosol, and the subsequent induction of Fas expression and cell death. Finally, we show that phagosomal escape/intracellular bacterial burden regulate activation of the transcription factors sp1/sp3, leading to Fas expression and cell death. These data identify for the first time host cell signaling pathways that regulate the phagosomal escape of Francisella, leading to the induction of Fas and subsequent host cell death.
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spelling pubmed-27754082009-11-24 Akt and SHIP Modulate Francisella Escape from the Phagosome and Induction of the Fas-Mediated Death Pathway Rajaram, Murugesan V. S. Butchar, Jonathan P. Parsa, Kishore V. L. Cremer, Thomas J. Amer, Amal Schlesinger, Larry S. Tridandapani, Susheela PLoS One Research Article Francisella tularensis infects macrophages and escapes phago-lysosomal fusion to replicate within the host cytosol, resulting in host cell apoptosis. Here we show that the Fas-mediated death pathway is activated in infected cells and correlates with escape of the bacterium from the phagosome and the bacterial burden. Our studies also demonstrate that constitutive activation of Akt, or deletion of SHIP, promotes phago-lysosomal fusion and limits bacterial burden in the host cytosol, and the subsequent induction of Fas expression and cell death. Finally, we show that phagosomal escape/intracellular bacterial burden regulate activation of the transcription factors sp1/sp3, leading to Fas expression and cell death. These data identify for the first time host cell signaling pathways that regulate the phagosomal escape of Francisella, leading to the induction of Fas and subsequent host cell death. Public Library of Science 2009-11-20 /pmc/articles/PMC2775408/ /pubmed/19936232 http://dx.doi.org/10.1371/journal.pone.0007919 Text en Rajaram et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rajaram, Murugesan V. S.
Butchar, Jonathan P.
Parsa, Kishore V. L.
Cremer, Thomas J.
Amer, Amal
Schlesinger, Larry S.
Tridandapani, Susheela
Akt and SHIP Modulate Francisella Escape from the Phagosome and Induction of the Fas-Mediated Death Pathway
title Akt and SHIP Modulate Francisella Escape from the Phagosome and Induction of the Fas-Mediated Death Pathway
title_full Akt and SHIP Modulate Francisella Escape from the Phagosome and Induction of the Fas-Mediated Death Pathway
title_fullStr Akt and SHIP Modulate Francisella Escape from the Phagosome and Induction of the Fas-Mediated Death Pathway
title_full_unstemmed Akt and SHIP Modulate Francisella Escape from the Phagosome and Induction of the Fas-Mediated Death Pathway
title_short Akt and SHIP Modulate Francisella Escape from the Phagosome and Induction of the Fas-Mediated Death Pathway
title_sort akt and ship modulate francisella escape from the phagosome and induction of the fas-mediated death pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775408/
https://www.ncbi.nlm.nih.gov/pubmed/19936232
http://dx.doi.org/10.1371/journal.pone.0007919
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