TLRs and TIR domain-containing adaptor molecules. TLR1/2 and TLR2/6 utilize MyD88 and Mal as adaptors. TLR3 is dependent on TRIF for signaling. In the case of TLR4, four different adaptors, i.e., MyD88, Mal, TRIF, and TRAM, are involved, whereas TLR5, -7, -8, and -9 utilize only MyD88. The fifth adaptor, SARM, negatively regulates TRIF-dependent signaling. Overall, MyD88-dependent signaling induces proinflammatory cytokine production, whereas TRIF-dependent signaling stimulates a type I IFN response. In pDCs, stimulation of TLR7 or TLR9 induces type I IFN production by a mechanism dependent on MyD88. See text for further details.