Different members of the Toll-like receptor (TLR) family have evolved to recognize the distinct signatures left by pathogens, including the single-stranded (ss) and double-stranded nucleic acid genomes of viruses. In the case of plasmacytoid dendritic cells (pDCs), detection by TLRs culminates in a program of gene activation that helps these cells prime antiviral adaptive immune responses. The response to some viruses, such as influenza, is achieved without the need for replication of pDCs, which makes the process of immune activation less dependent on direct infection of pDCs. However, Lee et al. (see the Perspective by Reis e Sousa) show that for RNA viruses that generate replication intermediates in the cytosol, a direct indicator of viral replication is needed. In such cases, autophagy--the sequestering of organelles and long-lived proteins for delivery to the lysosome for degradation--helped unite ssRNA and its TLR sensing protein in the lysosome. It is not clear if this link between autophagy and innate recognition represents a broader means of facilitating immunity to pathogens.
- Eat Up to Meet Up
An unexpected function of autophagy (cellular self-digestion) is to unite RNA from infecting viruses with immune recognition molecules to trigger innate immune defenses.Permalink: