Figure 3.

Recognition of nucleic acids by innate immune cells triggers cytokine production. Nucleic acids or apoptotic particles can be taken up by B cells through the BCR, and immune complexes containing these antigens are taken up by monocytes, myeloid dendritic cells and pDCs through FcR-mediated recognition and internalization. Within endosomes, DNA and RNA then interact with TLR9 and TLR7, respectively. Viral RNA can also be delivered to endosomes by autophagosome formation in pDCs. The ligation of TLRs recruits the adaptor protein MyD88, which activates the NF-κB signaling cascade in B cells and leads to B cell activation and survival, as well as various effector functions. In pDCs, the recruitment of MyD88 preferentially triggers an IRF7-mediated signaling pathway, which initiates type I IFN production. In other cell types, MyD88 recruitment in late endosomes leads to inflammatory cytokine production. Cytosolic DNA and RNA can be recognized by sensors that, through adaptors, lead to type I IFN production. Cytosolic DNA can also be recognized by AIM2, which activates caspase-1, leading to proteolytic cleavage of pro–IL-1 and pro–IL-18 into active forms. Immune complexes may signal directly through both activating and inhibitory FcRs whose relative expression on the cell surface varies with cell activation status. How these positive and negative signals are integrated with each other and with TLR-mediated signals has not yet been fully elucidated. cDC, conventional dendritic cell; RLR, RIG-I like receptors; DDX41, a member of the DEXDc family of helicases; TBK1, TANK-binding kinase 1; ER, endoplasmic reticulum; Ig, immunoglobulin.