Type I interferon induction is detrimental during infection with the Whipple's disease bacterium, Tropheryma whipplei.
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Authors
Al Moussawi, KhatounGhigo, Eric
Kalinke, Ulrich
Alexopoulou, Lena
Mege, Jean-Louis
Desnues, Benoit
Issue Date
2010
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Show full item recordAbstract
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.Citation
Type I interferon induction is detrimental during infection with the Whipple's disease bacterium, Tropheryma whipplei. 2010, 6 (1):e1000722 PLoS Pathog.Affiliation
Université de la Méditerranée, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6236, Marseille, France.Journal
PLoS pathogensPubMed ID
20090833Type
ArticleLanguage
enISSN
1553-7374ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1000722
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