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Type I interferon induction is detrimental during infection with the Whipple's disease bacterium, Tropheryma whipplei.
Al Moussawi, Khatoun Ghigo, Eric Kalinke, Ulrich Alexopoulou, Lena Mege, Jean-Louis Desnues, Benoit
Al Moussawi, Khatoun
Ghigo, Eric
Kalinke, Ulrich
Alexopoulou, Lena
Mege, Jean-Louis
Desnues, Benoit
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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.
Citation
Type I interferon induction is detrimental during infection with the Whipple's disease bacterium, Tropheryma whipplei. 2010, 6 (1):e1000722 PLoS Pathog.
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Article
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en
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1553-7374