Friend or foe: RIG- I like receptors and diseases

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), which are pivotal sensors of RNA virus invasions, mediate the transcriptional induction of genes encoding type I interferons (IFNs) and proinflammatory cytokines, successfully establishing host antiviral immune response. A few excellent reviews have elaborated on the structural biology of RLRs and the antiviral mechanisms of RLR activation. In this review, we give a basic understanding of RLR biology and summarize recent findings of how RLR signaling cascade is strictly controlled by host regulatory mechanisms, which include RLR-interacting proteins, post-translational modifications and microRNAs (miRNAs). Furthermore, we pay particular attention to the relationship between RLRs and diseases, especially how RLRs participate in SARS-CoV-2, malaria or bacterial infections, how single-nucleotide polymorphisms (SNPs) or mutations in RLRs and antibodies against RLRs lead to autoinflammatory diseases and autoimmune diseases, and how RLRs are involved in anti-tumor immunity. These findings will provide insights and guidance for antiviral and immunomodulatory therapies targeting RLRs.