Which TLR does not signal through MyD88?

The Toll-like receptor (TLR) family plays a crucial role in the innate immune system, recognizing a variety of pathogens. Each TLR can trigger different signaling pathways, primarily through two adaptor proteins: MyD88 and TRIF.

TLR 3 is unique among the TLRs in that it does not utilize MyD88 for its signaling. Instead, TLR 3 primarily signals through the TRIF adaptor protein. This pathway is particularly important for the recognition of double-stranded RNA, a molecular pattern associated with viral infections. TLR 3's signaling through TRIF leads to the activation of pathways that result in the production of type I interferons and pro-inflammatory cytokines.

In contrast, TLR 2, TLR 4, and TLR 6 all signal through MyD88. TLR 2 recognizes a variety of bacterial components, TLR 4 is known for its role in recognizing lipopolysaccharides from Gram-negative bacteria, and TLR 6 is involved in the recognition of diacylated lipopeptides. All these receptors initiate MyD88-mediated signaling pathways, leading to inflammatory responses.

Understanding the distinct pathways that each TLR activates is critical for appreciating how the immune system