The MYD88 gene provides instructions for making a protein involved in signaling within immune cells. The MyD88 protein acts as an
adapter, connecting proteins that receive signals from outside the cell to the proteins that relay signals inside the cell. In
innate immunity, the MyD88 plays a pivotal role in immune cell activation through
Toll-like receptors (TLRs), which belong to large group of
pattern recognition receptors (PRR). In general, these receptors sense common patterns which are shared by various pathogens –
Pathogen-associated molecular pattern (PAMPs), or which are produced/released during cellular damage –
damage-associated molecular patterns (DAMPs).
TLRs are homologous to Toll receptors, which were first described in the ontogenesis of fruit flies
Drosophila, being responsible for dorso-ventral development. Hence,
TLRs have been proved in all animals from insects to mammals. TLRs are located either on the cellular surface (
TLR1,
TLR2,
TLR4,
TLR5,
TLR6) or within
endosomes (
TLR3,
TLR7,
TLR8,
TLR9) sensing extracellular or phagocytosed pathogens, respectively. TLRs are integral membrane glycoproteins with typical semicircular-shaped extracellular parts containing leucine-rich repeats responsible for ligand binding, and Intracellular parts containing
Toll-Interleukin receptor (TIR) domain. After ligand binding, all TLRs, apart from
TLR3, interact with adaptor protein MyD88. Another adaptor protein, which is activated by TLR3 and TLR4, is called
TIR domain-containing adapter-inducing IFN-β (TRIF). Subsequently, these proteins activate two important transcription factors: •
NF-κB is a dimeric protein responsible for expression of various inflammatory cytokines, chemokines and adhesion and costimulatory molecules, which in turn triggers acute inflammation and stimulation of adaptive immunity •
IRFs is a group of proteins responsible for expression of type I interferons setting the so-called antiviral state of a cell.
TLR7 and
TLR9 activate both NF-κB and IRF3 through MyD88-dependent and TRIF-independent pathway, respectively. Mutation in MYD88 at position 265 leading to a change from leucine to proline have been identified in many human lymphomas including ABC subtype of
diffuse large B-cell lymphoma and
Waldenström's macroglobulinemia. == Interactions ==