Type I interferon induction is detrimental during infection with the Whipple's disease bacterium, Tropheryma whipplei.
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.
Al Moussawi
Khatoun
K
Université de la Méditerranée, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6236, Marseille, France.
Ghigo
Eric
E
Kalinke
Ulrich
U
Alexopoulou
Lena
L
Mege
Jean-Louis
JL
Desnues
Benoit
B
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020869:Gene Expression Profiling; D020287:In Situ Nick-End Labeling; D050838:Interferon Regulatory Factor-3 / Q000276:immunology / Q000378:metabolism; D007370:Interferon Type I / Q000276:immunology* / Q000378:metabolism; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection; D054851:Tropheryma / Q000276:immunology / Q000378:metabolism; D008061:Whipple Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D050838:Interferon Regulatory Factor-3; D007370:Interferon Type I; C494233:Irf3 protein, mouse; D050794:STAT1 Transcription Factor