Cargando…

Francisella tularensis Outer Membrane Vesicles Participate in the Early Phase of Interaction With Macrophages

Francisella tularensis is known to release unusually shaped tubular outer membrane vesicles (OMV) containing a number of previously identified virulence factors and immunomodulatory proteins. In this study, we present that OMV isolated from the F. tularensis subsp. holarctica strain FSC200 enter rea...

Descripción completa

Detalles Bibliográficos
Autores principales: Pavkova, Ivona, Klimentova, Jana, Bavlovic, Jan, Horcickova, Lenka, Kubelkova, Klara, Vlcak, Erik, Raabova, Helena, Filimonenko, Vlada, Ballek, Ondrej, Stulik, Jiri
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554293/
https://www.ncbi.nlm.nih.gov/pubmed/34721352
http://dx.doi.org/10.3389/fmicb.2021.748706
_version_ 1784591765491154944
author Pavkova, Ivona
Klimentova, Jana
Bavlovic, Jan
Horcickova, Lenka
Kubelkova, Klara
Vlcak, Erik
Raabova, Helena
Filimonenko, Vlada
Ballek, Ondrej
Stulik, Jiri
author_facet Pavkova, Ivona
Klimentova, Jana
Bavlovic, Jan
Horcickova, Lenka
Kubelkova, Klara
Vlcak, Erik
Raabova, Helena
Filimonenko, Vlada
Ballek, Ondrej
Stulik, Jiri
author_sort Pavkova, Ivona
collection PubMed
description Francisella tularensis is known to release unusually shaped tubular outer membrane vesicles (OMV) containing a number of previously identified virulence factors and immunomodulatory proteins. In this study, we present that OMV isolated from the F. tularensis subsp. holarctica strain FSC200 enter readily into primary bone marrow-derived macrophages (BMDM) and seem to reside in structures resembling late endosomes in the later intervals. The isolated OMV enter BMDM generally via macropinocytosis and clathrin-dependent endocytosis, with a minor role played by lipid raft-dependent endocytosis. OMVs proved to be non-toxic and had no negative impact on the viability of BMDM. Unlike the parent bacterium itself, isolated OMV induced massive and dose-dependent proinflammatory responses in BMDM. Using transmission electron microscopy, we also evaluated OMV release from the bacterial surface during several stages of the interaction of Francisella with BMDM. During adherence and the early phase of the uptake of bacteria, we observed numerous tubular OMV-like protrusions bulging from the bacteria in close proximity to the macrophage plasma membrane. This suggests a possible role of OMV in the entry of bacteria into host cells. On the contrary, the OMV release from the bacterial surface during its cytosolic phase was negligible. We propose that OMV play some role in the extracellular phase of the interaction of Francisella with the host and that they are involved in the entry mechanism of the bacteria into macrophages.
format Online
Article
Text
id pubmed-8554293
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-85542932021-10-30 Francisella tularensis Outer Membrane Vesicles Participate in the Early Phase of Interaction With Macrophages Pavkova, Ivona Klimentova, Jana Bavlovic, Jan Horcickova, Lenka Kubelkova, Klara Vlcak, Erik Raabova, Helena Filimonenko, Vlada Ballek, Ondrej Stulik, Jiri Front Microbiol Microbiology Francisella tularensis is known to release unusually shaped tubular outer membrane vesicles (OMV) containing a number of previously identified virulence factors and immunomodulatory proteins. In this study, we present that OMV isolated from the F. tularensis subsp. holarctica strain FSC200 enter readily into primary bone marrow-derived macrophages (BMDM) and seem to reside in structures resembling late endosomes in the later intervals. The isolated OMV enter BMDM generally via macropinocytosis and clathrin-dependent endocytosis, with a minor role played by lipid raft-dependent endocytosis. OMVs proved to be non-toxic and had no negative impact on the viability of BMDM. Unlike the parent bacterium itself, isolated OMV induced massive and dose-dependent proinflammatory responses in BMDM. Using transmission electron microscopy, we also evaluated OMV release from the bacterial surface during several stages of the interaction of Francisella with BMDM. During adherence and the early phase of the uptake of bacteria, we observed numerous tubular OMV-like protrusions bulging from the bacteria in close proximity to the macrophage plasma membrane. This suggests a possible role of OMV in the entry of bacteria into host cells. On the contrary, the OMV release from the bacterial surface during its cytosolic phase was negligible. We propose that OMV play some role in the extracellular phase of the interaction of Francisella with the host and that they are involved in the entry mechanism of the bacteria into macrophages. Frontiers Media S.A. 2021-10-15 /pmc/articles/PMC8554293/ /pubmed/34721352 http://dx.doi.org/10.3389/fmicb.2021.748706 Text en Copyright © 2021 Pavkova, Klimentova, Bavlovic, Horcickova, Kubelkova, Vlcak, Raabova, Filimonenko, Ballek and Stulik. https://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) and the copyright owner(s) 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
Pavkova, Ivona
Klimentova, Jana
Bavlovic, Jan
Horcickova, Lenka
Kubelkova, Klara
Vlcak, Erik
Raabova, Helena
Filimonenko, Vlada
Ballek, Ondrej
Stulik, Jiri
Francisella tularensis Outer Membrane Vesicles Participate in the Early Phase of Interaction With Macrophages
title Francisella tularensis Outer Membrane Vesicles Participate in the Early Phase of Interaction With Macrophages
title_full Francisella tularensis Outer Membrane Vesicles Participate in the Early Phase of Interaction With Macrophages
title_fullStr Francisella tularensis Outer Membrane Vesicles Participate in the Early Phase of Interaction With Macrophages
title_full_unstemmed Francisella tularensis Outer Membrane Vesicles Participate in the Early Phase of Interaction With Macrophages
title_short Francisella tularensis Outer Membrane Vesicles Participate in the Early Phase of Interaction With Macrophages
title_sort francisella tularensis outer membrane vesicles participate in the early phase of interaction with macrophages
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554293/
https://www.ncbi.nlm.nih.gov/pubmed/34721352
http://dx.doi.org/10.3389/fmicb.2021.748706
work_keys_str_mv AT pavkovaivona francisellatularensisoutermembranevesiclesparticipateintheearlyphaseofinteractionwithmacrophages
AT klimentovajana francisellatularensisoutermembranevesiclesparticipateintheearlyphaseofinteractionwithmacrophages
AT bavlovicjan francisellatularensisoutermembranevesiclesparticipateintheearlyphaseofinteractionwithmacrophages
AT horcickovalenka francisellatularensisoutermembranevesiclesparticipateintheearlyphaseofinteractionwithmacrophages
AT kubelkovaklara francisellatularensisoutermembranevesiclesparticipateintheearlyphaseofinteractionwithmacrophages
AT vlcakerik francisellatularensisoutermembranevesiclesparticipateintheearlyphaseofinteractionwithmacrophages
AT raabovahelena francisellatularensisoutermembranevesiclesparticipateintheearlyphaseofinteractionwithmacrophages
AT filimonenkovlada francisellatularensisoutermembranevesiclesparticipateintheearlyphaseofinteractionwithmacrophages
AT ballekondrej francisellatularensisoutermembranevesiclesparticipateintheearlyphaseofinteractionwithmacrophages
AT stulikjiri francisellatularensisoutermembranevesiclesparticipateintheearlyphaseofinteractionwithmacrophages