Long Noncoding RNAs in Host–Pathogen Interactions

Long noncoding RNAs (lncRNAs) are key molecules that regulate gene expression in a variety of organisms. LncRNAs can drive different transcriptional and post-transcriptional events that impact cellular functions. Recent studies have identified many lncRNAs associated with immune cell development and activation; however, an understanding of their functional role in host immunity to infection is just emerging. Here, we provide a detailed and updated review of the functional roles of lncRNAs in regulating mammalian immune responses during host–pathogen interactions, because these functions may be either beneficial or detrimental to the host. With increased mechanistic insight into the roles of lncRNAs, it may be possible to design and/or improve lncRNA-based therapies to treat a variety of infectious and inflammatory diseases. LncRNAs are noncoding transcripts longer than 200 nucleotides that bind DNA, RNA, and proteins, and can regulate gene expression via diverse mechanisms. Mammalian hosts and pathogens encode lncRNAs that can regulate host–pathogen interactions; these have either beneficial or detrimental roles for host survival. In human, the host-encoded lncRNA nuclear enriched abundant transcript-1 (NEAT1) can exert an antibacterial function during Salmonella infection by enhancing host immune gene expression. The host-encoded lncRNA-aconitate decarboxylase 1 (ACOD1) can promote viral replication by modulating cellular metabolism in both mouse [vesicular stomatitis virus (VSV) infection] and humans (influenza A/PR/8/34 virus infection). In mice, the host-encoded lncRNA-Lms3b can restrict VSV-induced innate immune responses by inactivating the retinoic acid-inducible gene I (RIG-I) signaling pathway.