ID: 103: Innate immune sensing of nucleic acids in airway epithelial cells compared to monocytic cells

Abstract

In the last decade mechanisms for innate immune sensing of pathogen and self nucleic acids have been defined. For cytosolic sensing of DNA, the adaptor protein STING has a central role, operating downstream of DNA sensors such as cGAS and IFI16 to mediate transcription factor activation and cytokine and interferon induction. However most of the work in defining cytosolic DNA sensing pathways has been done in monocytic cells, while sensing mechanisms in other frontline sensing cells such as airway epithelial cells have been less well defined. Thus here we analysed the innate immune response of human airway epithelial cell line models to RNA and DNA, in comparison to a human monocytic cell line. Our results show that in both monocytic and epithelial cells the innate immune response to RNA virus and dsRNA was promptly activated. However compared to monocytic cells, A549 and BEAS-2B epithelial cells failed to produce inflammatory cytokines and interferons in response to DNA viruses and dsDNA. These cells lacked expression of IFI16 or STING, but did express cGAS. Ectopic expression of STING restored the DNA response in A549 cells, in a cGAS-dependent manner. In contrast to A549 and BEAS-2B cells, the hTERT-immortalised normal airway epithelial cell line NuLi-1 did express IFI16, cGAS and STING, and responded to DNA viruses and DNA in a STING-dependent manner. These results highlight the loss of DNA responses in epithelial cell lines lacking STING, and have relevance in considering different cell models for innate sensing studies in airway epithelial cells.