Role of Trif in LPS- and dsRNA-induced upregulation of costimulatory molecules.

Activation of antigen presenting cells (APCs) by LPS or dsRNA results in heterodimerization of Trif/Tram (TLR4) or homodimerization of Trif (TLR3) leading to the subsequent activation of MAP kinases and NF-kB but also to activation of the IRF3 pathway. Activated IRF3 translocates to the nucleus and results in transcription of IFN-b. In turn IFN-b is secreted and activates type I IFN receptor (IRFRA1,2) in an atocrine or paracrine way. Activation of the type I IFN receptor results in the upregulation of costimulatory molecules such as CD40, CD80 and CD86 leading to optimal APC- T-cell interaction and subsequent T-cell activation.