%0 Generic %A van Lieshout M.H.P. %A S., Florquin %A C., vanʼt Veer %A de Vos A.F. %A van der Poll T. %D 2015 %T Supplementary Material for: TIR-Domain-Containing Adaptor-Inducing Interferon-β (TRIF) Mediates Antibacterial Defense during Gram-Negative Pneumonia by Inducing Interferon-γ %U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_TIR-Domain-Containing_Adaptor-Inducing_Interferon-_TRIF_Mediates_Antibacterial_Defense_during_Gram-Negative_Pneumonia_by_Inducing_Interferon-_/5128099 %R 10.6084/m9.figshare.5128099.v1 %2 https://ndownloader.figshare.com/files/8716120 %2 https://ndownloader.figshare.com/files/8716123 %2 https://ndownloader.figshare.com/files/8716126 %K Pneumonia %K Toll-like receptors %K Gram-negative sepsis %X Klebsiella pneumoniae is an important cause of Gram-negative pneumonia and sepsis. Mice deficient for TIR-domain-containing adaptor-inducing interferon-β (TRIF) demonstrate enhanced bacterial growth and dissemination during Klebsiella pneumonia. We show here that the impaired antibacterial defense of TRIF mutant mice is associated with absent interferon (IFN)-γ production in the lungs. IFN-γ production by splenocytes in response to K. pneumoniae in vitro was critically dependent on Toll-like receptor 4 (TLR4), the common TLR adaptor myeloid differentiation primary response gene (MyD88) and TRIF. Reconstitution of TRIF mutant mice with recombinant IFN-γ via the airways reduced bacterial loads in lungs and distant body sites to levels measured in wild-type mice, and partially restored pulmonary cytokine levels. The IFN-γ-induced, improved, enhanced antibacterial response in TRIF mutant mice occurred at the expense of increased hepatocellular injury. These data indicate that TRIF mediates antibacterial defense during Gram-negative pneumonia, at least in part, by inducing IFN-γ at the primary site of infection. %I Karger Publishers