PRRs are watching you: Localization of innate sensing and signaling regulators

Abstract

To prevent the spread of infection, an invading pathogen must first be recognized by the innate immune system. Host pattern recognition receptors detect distinct pathogen-associated molecules and induce the transcription and release of interferon and inflammatory molecules to resolve infection. Unlike infections with pathogens that replicate autonomously from the host, viral infections blur the boundaries of self and non-self. Differentiation of host from virus is achieved by restricting localization of host nucleic acids and by placing pattern recognition receptors in specific subcellular compartments. Within this review, we discuss how several families of pattern recognition receptors act to provide a comprehensive surveillance network that has the potential to induce interferon expression in response to any viral infection.

Keywords: Innate immunity; Interferon; RIG-I-like Receptors; STING; Toll-like Receptors; cGAS.

Figure 1. Multiple organelles initiate signal transduction that lead to type I IFN expression

Viruses can enter most cells through the endocytic pathway or by crossing the plasma membrane. TLRs detect viral genomes in endosomes. Once in the cytoplasm, genomic viral RNA (vRNA) can be detected by the RLRs and activate type-I IFN through MAVS, located on mitochondria and ER membranes. Genomic viral DNA (vDNA) is detected in the cytoplasm by cGAS or in the nucleus by IFI16. Both sensors activate STING to induce type-I IFNs. cGAS and RLRs can also detect viral replication intermediates in viral factories. All pathways activate the IRF and NF-kB transcription factors to stimulate IFNB transcription.