Location, Location, Location: Is Membrane Partitioning Everything When It Comes to Innate Immune Activation?

Figure 2

Activation of TLRs in endosomes. Various TLRs recognize microbial patterns within the endosome. TLR7 and 8 recognize ssRNA, whereas TLR9 recognises CpG DNA. As nucleic acid recognition bears a potential source for the induction of autoimmunity, TLR7 and 9 exist in a full-length and truncated version, where the ectodomain is cleaved. Only the endosomally processed forms are capable to recruit MyD88 and to induce signaling. Transport from the endoplasmatic reticulum (ER) is facilitated by UNC93B1 (a). Ligation of TLR7 by ssRNA leads to clustering within a lipid raft at the endosomal membrane and activation of intracellular signaling cascades that lead via NF-κB to production and secretion of proinflammatory cytokines (b).