Type I interferon induction is detrimental during infection with the Whipple's disease bacterium, Tropheryma whipplei.

2.50
Hdl Handle:
http://hdl.handle.net/10033/96001
Title:
Type I interferon induction is detrimental during infection with the Whipple's disease bacterium, Tropheryma whipplei.
Authors:
Al Moussawi, Khatoun; Ghigo, Eric; Kalinke, Ulrich ( 0000-0003-0503-9564 ) ; Alexopoulou, Lena; Mege, Jean-Louis; Desnues, Benoit
Abstract:
Macrophages are the first line of defense against pathogens. Upon infection macrophages usually produce high levels of proinflammatory mediators. However, macrophages can undergo an alternate polarization leading to a permissive state. In assessing global macrophage responses to the bacterial agent of Whipple's disease, Tropheryma whipplei, we found that T. whipplei induced M2 macrophage polarization which was compatible with bacterial replication. Surprisingly, this M2 polarization of infected macrophages was associated with apoptosis induction and a functional type I interferon (IFN) response, through IRF3 activation and STAT1 phosphorylation. Using macrophages from mice deficient for the type I IFN receptor, we found that this type I IFN response was required for T. whipplei-induced macrophage apoptosis in a JNK-dependent manner and was associated with the intracellular replication of T. whipplei independently of JNK. This study underscores the role of macrophage polarization in host responses and highlights the detrimental role of type I IFN during T. whipplei infection.
Affiliation:
Université de la Méditerranée, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6236, Marseille, France.
Citation:
Type I interferon induction is detrimental during infection with the Whipple's disease bacterium, Tropheryma whipplei. 2010, 6 (1):e1000722 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
2010
URI:
http://hdl.handle.net/10033/96001
DOI:
10.1371/journal.ppat.1000722
PubMed ID:
20090833
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorAl Moussawi, Khatounen
dc.contributor.authorGhigo, Ericen
dc.contributor.authorKalinke, Ulrichen
dc.contributor.authorAlexopoulou, Lenaen
dc.contributor.authorMege, Jean-Louisen
dc.contributor.authorDesnues, Benoiten
dc.date.accessioned2010-04-08T13:55:06Zen
dc.date.available2010-04-08T13:55:06Zen
dc.date.issued2010en
dc.identifier.citationType I interferon induction is detrimental during infection with the Whipple's disease bacterium, Tropheryma whipplei. 2010, 6 (1):e1000722 PLoS Pathog.en
dc.identifier.issn1553-7374en
dc.identifier.pmid20090833en
dc.identifier.doi10.1371/journal.ppat.1000722en
dc.identifier.urihttp://hdl.handle.net/10033/96001en
dc.description.abstractMacrophages are the first line of defense against pathogens. Upon infection macrophages usually produce high levels of proinflammatory mediators. However, macrophages can undergo an alternate polarization leading to a permissive state. In assessing global macrophage responses to the bacterial agent of Whipple's disease, Tropheryma whipplei, we found that T. whipplei induced M2 macrophage polarization which was compatible with bacterial replication. Surprisingly, this M2 polarization of infected macrophages was associated with apoptosis induction and a functional type I interferon (IFN) response, through IRF3 activation and STAT1 phosphorylation. Using macrophages from mice deficient for the type I IFN receptor, we found that this type I IFN response was required for T. whipplei-induced macrophage apoptosis in a JNK-dependent manner and was associated with the intracellular replication of T. whipplei independently of JNK. This study underscores the role of macrophage polarization in host responses and highlights the detrimental role of type I IFN during T. whipplei infection.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshApoptosisen
dc.subject.meshBlotting, Westernen
dc.subject.meshEnzyme-Linked Immunosorbent Assayen
dc.subject.meshFluorescent Antibody Techniqueen
dc.subject.meshGene Expressionen
dc.subject.meshGene Expression Profilingen
dc.subject.meshIn Situ Nick-End Labelingen
dc.subject.meshInterferon Regulatory Factor-3en
dc.subject.meshInterferon Type Ien
dc.subject.meshMacrophage Activationen
dc.subject.meshMacrophagesen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMice, Knockouten
dc.subject.meshOligonucleotide Array Sequence Analysisen
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen
dc.subject.meshSTAT1 Transcription Factoren
dc.subject.meshSignal Transductionen
dc.subject.meshTransfectionen
dc.subject.meshTropherymaen
dc.subject.meshWhipple Diseaseen
dc.titleType I interferon induction is detrimental during infection with the Whipple's disease bacterium, Tropheryma whipplei.en
dc.typeArticleen
dc.contributor.departmentUniversité de la Méditerranée, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6236, Marseille, France.en
dc.identifier.journalPLoS pathogensen

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