Activation of cytosolic DNA sensing in NCM460 intestinal epithelial cells induces antiviral factors that restrict HIV infection in macrophages.

Introduction: The gastrointestinal tract is an important site of HIV persistence and contains susceptible target cells, including macrophages. Crosstalk between intestinal epithelial cells and macrophages may contribute to mucosal innate defense. Methods: NCM460 human intestinal epithelial cells were transfected with poly(dA). Expression and production of interferons, interferon-stimulated genes, and CC chemokines were assessed by quantitative RT-PCR, western blotting, and ELISA. Primary human macrophages were treated with conditioned supernatants from NCM460 cells, and HIV infection was assessed using cytopathic effects, luciferase activity, and HIV Gag RNA expression. Results: Poly(dA) induced IFN-β, IFN-λ1, IFN-λ2/3, ISG15, viperin, OAS1, RANTES, and MIP-1α in NCM460 cells. Supernatants from poly(dA)-stimulated NCM460 cells induced GBP5, viperin, and MX2 in primary macrophages and significantly inhibited HIV infection. Discussion: Activation of cytosolic DNA sensing in intestinal epithelial cells induces soluble antiviral factors that enhance innate antiviral responses in macrophages and may contribute to mucosal defense against HIV.