Research ArticleImmunology

Innate immune memory and homeostasis may be conferred through crosstalk between the TLR3 and TLR7 pathways

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Sci. Signal.  12 Jul 2016:
Vol. 9, Issue 436, pp. ra70
DOI: 10.1126/scisignal.aac9340

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Modeling immune responses

During the course of an infection, the host is often exposed to numerous pathogen-derived stimuli at different times. Macrophages are activated through Toll-like receptor 3 (TLR3) by double-stranded viral RNA, whereas single-stranded viral RNA stimulates TLR7. Stimulation of TLR3 before TLR7 leads to the synergistically increased production of cytokines as part of the immune response. Liu et al. analyzed cytokine mRNA abundances in macrophages exposed to TLR3 and TLR7 stimuli in different orders and after different time intervals. Mathematical modeling of these data predicted and experiments validated that crosstalk occurred between both pathways and showed how the JAK-STAT pathway was required for TLR3 signaling to induce synergistic responses to subsequent TLR7 stimulation. This computational modeling approach may be applied to study other immune signaling pathways to uncover potential crosstalk mechanisms.