Jump to Main Content
DNA-triggered innate immune responses are propagated by gap junction communication
- Patel, Suraj J., King, Kevin R., Casali, Monica, Yarmush, Martin L.
- Proceedings of the National Academy of Sciences of the United States of America 2009 v.106 no.31 pp. 12867-12872
- DNA, gap junctions, image analysis, immune response, innate immunity, pathogens, signal transduction, tumor necrosis factor-alpha
- Cells respond to infection by sensing pathogens and communicating danger signals to noninfected neighbors; however, little is known about this complex spatiotemporal process. Here we show that activation of the innate immune system by double-stranded DNA (dsDNA) triggers intercellular communication through a gap junction-dependent signaling pathway, recruiting colonies of cells to collectively secrete antiviral and inflammatory cytokines for the propagation of danger signals across the tissue at large. By using live-cell imaging of a stable IRF3-sensitive GFP reporter, we demonstrate that dsDNA sensing leads to multicellular colonies of IRF3-activated cells that express the majority of secreted cytokines, including IFNβ and TNFα. Inhibiting gap junctions decreases dsDNA-induced IRF3 activation, cytokine production, and the resulting tissue-wide antiviral state, indicating that this immune response propagation pathway lies upstream of the paracrine action of secreted cytokines and may represent a host-derived mechanism for evading viral antiinterferon strategies.