Legionella pneumophila Strain 130b Evades Macrophage Cell Death Independent of the Effector SidF in the Absence of Flagellin
Autor: | James E Vince, Qingqing Han, Gilu Abraham, Richard A. Flavell, Azadeh Seidi, Adam Vogrin, Seth L. Masters, Stéphane Hunot, Gerald W. Dorn, Mary Speir, Thomas Naderer |
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Přispěvatelé: | HAL UPMC, Gestionnaire, Monash University [Clayton], Yale School of Medicine [New Haven, Connecticut] (YSM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Washington University in Saint Louis (WUSTL), The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, Yale University School of Medicine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP) |
Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Microbiology (medical) Programmed cell death 030106 microbiology Immunology [SDV.BC]Life Sciences [q-bio]/Cellular Biology Legionella pneumophila Microbiology live-cell imaging 03 medical and health sciences Macrophage pneumonia bacteria [SDV.BC] Life Sciences [q-bio]/Cellular Biology Original Research biology Effector pyroptosis Intrinsic apoptosis Pyroptosis biology.organism_classification Bacterial effector protein [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology infection respiratory tract diseases mitochondria 030104 developmental biology Infectious Diseases caspases biology.protein [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Flagellin |
Zdroj: | Frontiers in Cellular and Infection Microbiology Frontiers in Cellular and Infection Microbiology, 2017, 7, pp.35. ⟨10.3389/fcimb.2017.00035⟩ Frontiers in Cellular and Infection Microbiology, Frontiers, 2017, 7, pp.35. ⟨10.3389/fcimb.2017.00035⟩ |
ISSN: | 2235-2988 |
DOI: | 10.3389/fcimb.2017.00035 |
Popis: | International audience; 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. |
Databáze: | OpenAIRE |
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