IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection.
| Title: | IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection. |
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| Authors: | Wallet, Pierre1, Benaoudia, Sacha1, Mosnier, Amandine1, Lagrange, Brice1, Martin, Amandine1, Lindgren, Helena2, Golovliov, Igor2, Michal, Fanny1, Basso, Pauline3, Djebali, Sophia1, Provost, Angelina1, Allatif, Omran1, Meunier, Etienne4, Broz, Petr5, Yamamoto, Masahiro6, Py, Bénédicte F.1, Faudry, Eric3, Sjöstedt, Anders2, Henry, Thomas1 thomas.henry@inserm.fr |
| Source: | PLoS Pathogens. 10/3/2017, Vol. 13 Issue 10, p1-26. 26p. |
| Subject Terms: | *FRANCISELLA novicida, *INTERFERON gamma, *INFLAMMASOMES, *ANTIBACTERIAL agents, *INTERFERON inducers |
| Abstract: | Guanylate binding proteins (GBPs) are interferon-inducible proteins involved in the cell-intrinsic immunity against numerous intracellular pathogens. The molecular mechanisms underlying the potent antibacterial activity of GBPs are still unclear. GBPs have been functionally linked to the NLRP3, the AIM2 and the caspase-11 inflammasomes. Two opposing models are currently proposed to explain the GBPs-inflammasome link: i) GBPs would target intracellular bacteria or bacteria-containing vacuoles to increase cytosolic PAMPs release ii) GBPs would directly facilitate inflammasome complex assembly. Using Francisella novicida infection, we investigated the functional interactions between GBPs and the inflammasome. GBPs, induced in a type I IFN-dependent manner, are required for the F. novicida-mediated AIM2-inflammasome pathway. Here, we demonstrate that GBPs action is not restricted to the AIM2 inflammasome, but controls in a hierarchical manner the activation of different inflammasomes complexes and apoptotic caspases. IFN-γ induces a quantitative switch in GBPs levels and redirects pyroptotic and apoptotic pathways under the control of GBPs. Furthermore, upon IFN-γ priming, F. novicida-infected macrophages restrict cytosolic bacterial replication in a GBP-dependent and inflammasome-independent manner. Finally, in a mouse model of tularemia, we demonstrate that the inflammasome and the GBPs are two key immune pathways functioning largely independently to control F. novicida infection. Altogether, our results indicate that GBPs are the master effectors of IFN-γ-mediated responses against F. novicida to control antibacterial immune responses in inflammasome-dependent and independent manners. [ABSTRACT FROM AUTHOR] |
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| Items | – Name: Title Label: Title Group: Ti Data: IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Wallet%2C+Pierre%22">Wallet, Pierre</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Benaoudia%2C+Sacha%22">Benaoudia, Sacha</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Mosnier%2C+Amandine%22">Mosnier, Amandine</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Lagrange%2C+Brice%22">Lagrange, Brice</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Martin%2C+Amandine%22">Martin, Amandine</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Lindgren%2C+Helena%22">Lindgren, Helena</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Golovliov%2C+Igor%22">Golovliov, Igor</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Michal%2C+Fanny%22">Michal, Fanny</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Basso%2C+Pauline%22">Basso, Pauline</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Djebali%2C+Sophia%22">Djebali, Sophia</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Provost%2C+Angelina%22">Provost, Angelina</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Allatif%2C+Omran%22">Allatif, Omran</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Meunier%2C+Etienne%22">Meunier, Etienne</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Broz%2C+Petr%22">Broz, Petr</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Yamamoto%2C+Masahiro%22">Yamamoto, Masahiro</searchLink><relatesTo>6</relatesTo><br /><searchLink fieldCode="AR" term="%22Py%2C+Bénédicte+F%2E%22">Py, Bénédicte F.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Faudry%2C+Eric%22">Faudry, Eric</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Sjöstedt%2C+Anders%22">Sjöstedt, Anders</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Henry%2C+Thomas%22">Henry, Thomas</searchLink><relatesTo>1</relatesTo><i> thomas.henry@inserm.fr</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22PLoS+Pathogens%22">PLoS Pathogens</searchLink>. 10/3/2017, Vol. 13 Issue 10, p1-26. 26p. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22FRANCISELLA+novicida%22">FRANCISELLA novicida</searchLink><br />*<searchLink fieldCode="DE" term="%22INTERFERON+gamma%22">INTERFERON gamma</searchLink><br />*<searchLink fieldCode="DE" term="%22INFLAMMASOMES%22">INFLAMMASOMES</searchLink><br />*<searchLink fieldCode="DE" term="%22ANTIBACTERIAL+agents%22">ANTIBACTERIAL agents</searchLink><br />*<searchLink fieldCode="DE" term="%22INTERFERON+inducers%22">INTERFERON inducers</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Guanylate binding proteins (GBPs) are interferon-inducible proteins involved in the cell-intrinsic immunity against numerous intracellular pathogens. The molecular mechanisms underlying the potent antibacterial activity of GBPs are still unclear. GBPs have been functionally linked to the NLRP3, the AIM2 and the caspase-11 inflammasomes. Two opposing models are currently proposed to explain the GBPs-inflammasome link: i) GBPs would target intracellular bacteria or bacteria-containing vacuoles to increase cytosolic PAMPs release ii) GBPs would directly facilitate inflammasome complex assembly. Using Francisella novicida infection, we investigated the functional interactions between GBPs and the inflammasome. GBPs, induced in a type I IFN-dependent manner, are required for the F. novicida-mediated AIM2-inflammasome pathway. Here, we demonstrate that GBPs action is not restricted to the AIM2 inflammasome, but controls in a hierarchical manner the activation of different inflammasomes complexes and apoptotic caspases. IFN-γ induces a quantitative switch in GBPs levels and redirects pyroptotic and apoptotic pathways under the control of GBPs. Furthermore, upon IFN-γ priming, F. novicida-infected macrophages restrict cytosolic bacterial replication in a GBP-dependent and inflammasome-independent manner. Finally, in a mouse model of tularemia, we demonstrate that the inflammasome and the GBPs are two key immune pathways functioning largely independently to control F. novicida infection. Altogether, our results indicate that GBPs are the master effectors of IFN-γ-mediated responses against F. novicida to control antibacterial immune responses in inflammasome-dependent and independent manners. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of PLoS Pathogens is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1371/journal.ppat.1006630 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 26 StartPage: 1 Subjects: – SubjectFull: FRANCISELLA novicida Type: general – SubjectFull: INTERFERON gamma Type: general – SubjectFull: INFLAMMASOMES Type: general – SubjectFull: ANTIBACTERIAL agents Type: general – SubjectFull: INTERFERON inducers Type: general Titles: – TitleFull: IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Wallet, Pierre – PersonEntity: Name: NameFull: Benaoudia, Sacha – PersonEntity: Name: NameFull: Mosnier, Amandine – PersonEntity: Name: NameFull: Lagrange, Brice – PersonEntity: Name: NameFull: Martin, Amandine – PersonEntity: Name: NameFull: Lindgren, Helena – PersonEntity: Name: NameFull: Golovliov, Igor – PersonEntity: Name: NameFull: Michal, Fanny – PersonEntity: Name: NameFull: Basso, Pauline – PersonEntity: Name: NameFull: Djebali, Sophia – PersonEntity: Name: NameFull: Provost, Angelina – PersonEntity: Name: NameFull: Allatif, Omran – PersonEntity: Name: NameFull: Meunier, Etienne – PersonEntity: Name: NameFull: Broz, Petr – PersonEntity: Name: NameFull: Yamamoto, Masahiro – PersonEntity: Name: NameFull: Py, Bénédicte F. – PersonEntity: Name: NameFull: Faudry, Eric – PersonEntity: Name: NameFull: Sjöstedt, Anders – PersonEntity: Name: NameFull: Henry, Thomas IsPartOfRelationships: – BibEntity: Dates: – D: 03 M: 10 Text: 10/3/2017 Type: published Y: 2017 Identifiers: – Type: issn-print Value: 15537366 Numbering: – Type: volume Value: 13 – Type: issue Value: 10 Titles: – TitleFull: PLoS Pathogens Type: main |
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