Latent TLR9 resides in the ER and traffics to endosomes where it is processed to become active. Trafficking is UNC-93B-dependent. Cytoplasmic CpG DNA engulfed in endolysosomes associates with TLR9 which triggers recruitment of a signaling complex consisting of MyD88, IRAK4 and TRAF6. TRAF6 in turn activates TAK1, and subsequently MAPK and the IKK complex (IKKα, IKKβ, and IKKγ) to activate NF-κB. NF-κB and MAPK regulates inflammatory cytokine expression. IRAK4 also activates TRAF3 and IRAK1, which catalyzes IRF7 phosphorylation to induce type I IFNs expression.