Klebsiella pneumoniae causes extensive lung damage. TLR signaling involves adaptors TRIF and MyD88. However, the relative contribution of TRIF and MyD88 signaling in host defense against pulmonary K. pneumoniae infection has not been elucidated. Therefore, we investigated the role of TRIF and MyD88 in K. pneumoniae pneumonia. TRIF(-/-) mice infected with K. pneumoniae showed impaired survival a...

Allergic asthma is a chronic pulmonary inflammatory disease characterized by reversible airway obstruction, hyperresponsiveness and eosinophils infiltration. Toll-like receptors (TLRs) signaling are closely associated with asthma and have emerged as a novel therapeutic target in allergic disease. The functions of TLR3 and TLR4 in allergic airway inflammation have been studied; however, the prec...

BACKGROUND The innate immune responses to virus infection are initiated by either Toll-like receptors (TLR3/7/8/9) or cytoplasmic double-stranded RNA (dsRNA)-recognizing RNA helicases RIG-I and MDA5. To avoid causing injury to the host, these signaling pathways must be switched off in time by negative regulators. METHODOLOGY/PRINCIPAL FINDINGS Through yeast-two hybrid screening, we found that...

TRIF [TIR (Toll/interleukin-1 receptor) domain-containing adaptor protein inducing interferon beta; also known as TICAM-1 (TIR-containing adaptor molecule-1)] is a key adaptor for TLR3 (Toll-like receptor 3)- and TLR4-mediated signalling. We have performed a detailed annotation of the human TRIF gene and fine analysis of the basal and inducible promoter elements lying 5' to the site of initiati...

BACKGROUND & AIMS Toll-like receptor 4 (TLR4) signaling is activated through 2 adaptor proteins: MyD88 and TIR-domain containing adaptor-inducing interferon-β (TRIF). TLR4 and MyD88 are crucial in nonalcoholic steatohepatitis (NASH) and fibrosis. However, the role of TRIF in TLR4-mediated NASH and fibrosis has been elusive. This study investigated the differential roles of TRIF in hepatic steat...

Campylobacter jejuni is an important cause of human enteritis and has been linked to the development of autoimmune diseases. Recently we showed that infection of murine dendritic cells (DCs) with C. jejuni resulted in DC activation and induction of Campylobacter-specific Th1-effector responses. Toll-like receptor (TLR) signaling through myeloid differentiation factor 88 (MyD88) and/or Toll-inte...

NK cells play essential roles in eliminating virally infected cells and tumor cells. Polyinosinic-polycytidylic acid (poly I:C), a double-stranded RNA analog recognized by melanoma-differentiation associated gene 5 (MDA5) and TLR3, activates NK cells in vivo. MDA5 and TLR3 signal through distinct adaptor molecules, IFN-promoter stimulator-1 (IPS-1) and Toll/IL-1R domain-containing adaptor induc...

BACKGROUND Toll-like receptors (TLRs) have a central role in the recognition of pathogens and the initiation of the innate immune response. Myeloid differentiation primary-response gene 88 (MyD88) and TIR-domain-containing adaptor protein inducing IFNbeta (TRIF) are regarded as the key signaling adaptor proteins for TLRs. Melioidosis, which is endemic in SE-Asia, is a severe infection caused by...

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 here show that the impaired antibacterial defense of TRIF mutant mice is associated with absent interferon (IFN)-γ production in the lungs. IFN-γ pr...

We previously showed that monophosphoryl lipid A (MLA) activates TLR4 in dendritic cells (DCs) in a Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF)-biased manner: MLA produced from Salmonella minnesota Re595 induced signaling events and expression of gene products that were primarily TRIF dependent, whereas MyD88-dependent signaling was impaired. Moreover, when tested in TRIF-intact/...