The relative roles of the endosomal TLR3/7/8 versus the intracellular RNA helicases RIG-I and MDA5 in viral infection is much debated. We investigated the roles of each pattern recognition receptor in rhinovirus infection using primary bronchial epithelial cells. TLR3 was constitutively expressed; however, RIG-I and MDA5 were inducible by 8-12 h following rhinovirus infection. Bronchial epithel...

PKC has been shown to play a key role in the effect of the Gram-negative bacterial product LPS; however, the target for PKC in LPS signaling is unknown. LPS signaling is mediated by Toll-like receptor 4, which uses four adapter proteins, MyD88, MyD88 adapter-like (Mal), Toll IL-1R domain-containing adapter inducing IFN(Trif), and Trif-related adapter molecule (TRAM). Here we show that TRAM is t...

Hepatitis C NS3/4A protease is a prime therapeutic target that is responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A, and 5A5B and two host cell adaptor proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host cell cleavage sites were determined and compared to the crystal structures of viral substrates. Two distinct ...

Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar leve...

The immune response plays a key role in enhancing the therapeutic activity of oncolytic virotherapies. However, to date, investigators have relied on inherent interactions between the virus and the immune system, often coupled to the expression of a single cytokine transgene. Recently, the importance of TLR activation in mediating adaptive immunity has been demonstrated. We therefore sought to ...

Abstract Innate immune sensing of microbial and endogenous ligands by Toll-like receptor (TLR) 4 drives inflammation antimicrobial mechanisms. While critical for host defense against pathogens, unchecked TLR4 activation causes organ damage chronic disease. Molecular mechanisms that drive versus turn off activity are being pursued as potential targets preventing treating infections inflammation-...

Abstract Improved vaccine adjuvants are needed to address infectious diseases, cancer, and future pandemics. Toll-like receptors (TLRs) have been researched as targets of because they modulate the innate immune system activate adaptive immunity. TLR-based induce cross-presentation exogenous antigens CD8 T lymphocytes. TLR4 signaling recruits adapters myeloid differentiation marker 88 (MyD88), w...

Bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) can be activated by type I IFNs, TLR ago-nists, viruses, and bacteria to increase hematopoiesis. In this study, we report that endotoxin treatment in vivo induces TLR4, MyD88, and Toll/IL-1 resistance domain-containing adaptor-inducing IFN-b (TRIF)-dependent expansion of BM HSPCs. Bacterial infection by Staphylococcus aureus or ce...

Innate immune response plays a critical role in controlling invading pathogens, but such an immune response must be tightly regulated. Insufficient or overactivated immune responses may lead to harmful or even fatal consequences. To dissect the complex host-parasite interactions and the molecular mechanisms underlying innate immune responses to infections, here we investigate the role of FOS-li...