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Legionella pneumophila Strain 130b Evades Macrophage Cell Death Independent of the Effector SidF in the Absence of Flagellin
The human pathogen Legionella pneumophila must evade host cell death signaling to enable replication in lung macrophages and to cause disease. After bacterial growth, however, L. pneumophila is thought to induce apoptosis during egress from macrophages. The bacterial effector protein, SidF, has been...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311068/ https://www.ncbi.nlm.nih.gov/pubmed/28261564 http://dx.doi.org/10.3389/fcimb.2017.00035 |
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author | Speir, Mary Vogrin, Adam Seidi, Azadeh Abraham, Gilu Hunot, Stéphane Han, Qingqing Dorn, Gerald W. Masters, Seth L. Flavell, Richard A. Vince, James E. Naderer, Thomas |
author_facet | Speir, Mary Vogrin, Adam Seidi, Azadeh Abraham, Gilu Hunot, Stéphane Han, Qingqing Dorn, Gerald W. Masters, Seth L. Flavell, Richard A. Vince, James E. Naderer, Thomas |
author_sort | Speir, Mary |
collection | PubMed |
description | The human pathogen Legionella pneumophila must evade host cell death signaling to enable replication in lung macrophages and to cause disease. After bacterial growth, however, L. pneumophila is thought to induce apoptosis during egress from macrophages. The bacterial effector protein, SidF, has been shown to control host cell survival and death by inhibiting pro-apoptotic BNIP3 and BCL-RAMBO signaling. Using live-cell imaging to follow the L. pneumophila-macrophage interaction, we now demonstrate that L. pneumophila evades host cell apoptosis independent of SidF. In the absence of SidF, L. pneumophila was able to replicate, cause loss of mitochondria membrane potential, kill macrophages, and establish infections in lungs of mice. Consistent with this, deletion of BNIP3 and BCL-RAMBO did not affect intracellular L. pneumophila replication, macrophage death rates, and in vivo bacterial virulence. Abrogating mitochondrial cell death by genetic deletion of the effectors of intrinsic apoptosis, BAX, and BAK, or the regulator of mitochondrial permeability transition pore formation, cyclophilin-D, did not affect bacterial growth or the initial killing of macrophages. Loss of BAX and BAK only marginally limited the ability of L. pneumophila to efficiently kill all macrophages over extended periods. L. pneumophila induced killing of macrophages was delayed in the absence of capsase-11 mediated pyroptosis. Together, our data demonstrate that L. pneumophila evades host cell death responses independently of SidF during replication and can induce pyroptosis to kill macrophages in a timely manner. |
format | Online Article Text |
id | pubmed-5311068 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53110682017-03-03 Legionella pneumophila Strain 130b Evades Macrophage Cell Death Independent of the Effector SidF in the Absence of Flagellin Speir, Mary Vogrin, Adam Seidi, Azadeh Abraham, Gilu Hunot, Stéphane Han, Qingqing Dorn, Gerald W. Masters, Seth L. Flavell, Richard A. Vince, James E. Naderer, Thomas Front Cell Infect Microbiol Microbiology The human pathogen Legionella pneumophila must evade host cell death signaling to enable replication in lung macrophages and to cause disease. After bacterial growth, however, L. pneumophila is thought to induce apoptosis during egress from macrophages. The bacterial effector protein, SidF, has been shown to control host cell survival and death by inhibiting pro-apoptotic BNIP3 and BCL-RAMBO signaling. Using live-cell imaging to follow the L. pneumophila-macrophage interaction, we now demonstrate that L. pneumophila evades host cell apoptosis independent of SidF. In the absence of SidF, L. pneumophila was able to replicate, cause loss of mitochondria membrane potential, kill macrophages, and establish infections in lungs of mice. Consistent with this, deletion of BNIP3 and BCL-RAMBO did not affect intracellular L. pneumophila replication, macrophage death rates, and in vivo bacterial virulence. Abrogating mitochondrial cell death by genetic deletion of the effectors of intrinsic apoptosis, BAX, and BAK, or the regulator of mitochondrial permeability transition pore formation, cyclophilin-D, did not affect bacterial growth or the initial killing of macrophages. Loss of BAX and BAK only marginally limited the ability of L. pneumophila to efficiently kill all macrophages over extended periods. L. pneumophila induced killing of macrophages was delayed in the absence of capsase-11 mediated pyroptosis. Together, our data demonstrate that L. pneumophila evades host cell death responses independently of SidF during replication and can induce pyroptosis to kill macrophages in a timely manner. Frontiers Media S.A. 2017-02-16 /pmc/articles/PMC5311068/ /pubmed/28261564 http://dx.doi.org/10.3389/fcimb.2017.00035 Text en Copyright © 2017 Speir, Vogrin, Seidi, Abraham, Hunot, Han, Dorn II, Masters, Flavell, Vince and Naderer. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Speir, Mary Vogrin, Adam Seidi, Azadeh Abraham, Gilu Hunot, Stéphane Han, Qingqing Dorn, Gerald W. Masters, Seth L. Flavell, Richard A. Vince, James E. Naderer, Thomas Legionella pneumophila Strain 130b Evades Macrophage Cell Death Independent of the Effector SidF in the Absence of Flagellin |
title | Legionella pneumophila Strain 130b Evades Macrophage Cell Death Independent of the Effector SidF in the Absence of Flagellin |
title_full | Legionella pneumophila Strain 130b Evades Macrophage Cell Death Independent of the Effector SidF in the Absence of Flagellin |
title_fullStr | Legionella pneumophila Strain 130b Evades Macrophage Cell Death Independent of the Effector SidF in the Absence of Flagellin |
title_full_unstemmed | Legionella pneumophila Strain 130b Evades Macrophage Cell Death Independent of the Effector SidF in the Absence of Flagellin |
title_short | Legionella pneumophila Strain 130b Evades Macrophage Cell Death Independent of the Effector SidF in the Absence of Flagellin |
title_sort | legionella pneumophila strain 130b evades macrophage cell death independent of the effector sidf in the absence of flagellin |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311068/ https://www.ncbi.nlm.nih.gov/pubmed/28261564 http://dx.doi.org/10.3389/fcimb.2017.00035 |
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