type i interferon induction is detrimental during infection with the whipples disease bacterium, tropheryma whippleii型干扰素诱导是有害的细菌感染惠普尔氏病期间,tropheryma whipplei.pdfVIP

Type I Interferon Induction Is Detrimental during Infection with the Whipple’s Disease Bacterium, Tropheryma whipplei 1 1 2¤ 3 1 Khatoun Al Moussawi , Eric Ghigo , Ulrich Kalinke , Lena Alexopoulou , Jean-Louis Mege , Benoit Desnues1* ´ ´ ´ ´ 1 Universite de la Mediterranee, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 6236, Marseille, France, 2 Paul-Ehrlich-Institut, Langen, Germany, ´ ´ 3 Center of Immunology Marseille-Luminy, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 6102, Institut National de la Sante et de la Recherche ´ ´ ´ ´ ´ Medicale U631, Universite de la Mediterranee Unite Mixte de Recherche 6546, Campus of Luminy, Case 906, Marseille, France 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