title: TIR-Domain-Containing Adaptor-Inducing Interferon-β (TRIF) Mediates Antibacterial Defense during Gram-Negative Pneumonia by Inducing Interferon-x03B3.
abstract: 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)-x03B3; production in the lungs. IFN-x03B3; 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-x03B3; 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-x03B3;-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-x03B3; at the primary site of infection.
authors.affiliation: Center of Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Miriam H P
authors.initials: MH
authors.lastname: van Lieshout
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Cornelis
authors.initials: C
authors.lastname: Vanʼt Veer
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology*; D000818:Animals; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D007710:Klebsiella Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D007371:Interferon-gamma; C476286:Ticam1 protein, mouse