IL-1B signaling in dendritic cells induces antiviral interferon responses

Activation of interferon-stimulated gene (ISG) responses is critical for control of viral infection. We recently identified that stimulation of the NLRP3 inflammasome and mobilization of the inflammatory cytokine IL-1β act as critical host restrictive pathways against West Nile virus (WNV) in a mechanism dependent on the regulation of ISGs. In order to define the mechanism by which IL-1β regulates these antiviral immune programs, we utilized global transcriptome analysis in myeloid cells, known targets of WNV replication to define gene signatures required for IL-1β driven antiviral responses. Surprisingly, we found IL-1β dependent activation of interferon-beta (IFN-β) and ISGs at late times following IL-1β treatment. Expression of these antiviral innate immune genes was found to be dependent on activation of IRF3 and appears to reflect a general shift in IL-1β signaling from an inflammatory response early following treatment to an anti-inflammatory type-I IFN mediated response at later times post-treatment. These data demonstrate that inflammatory and antiviral signals integrate to control viral infection. Strategies to co-opt these cytokine activated antiviral signatures can act as novel targeted therapeutic strategies tailored specifically to individual pathogens. WT or IL-1R KO BMDCs were either mock-treated or pre-treated with 100 ng IL-1b for 24 hours. Cells were then either mock-infected or infected with WNV at an MOI of 2.5. Both mock and WNV-infected samples were harvested at 24 and 48 hours. WT BMDCs were also treated with IL-1b for 24 or 48 hours before harvest. All samples were run in triplicate. Total RNA was run on Agilent 4x44 mouse microarray Please note that the sample titles represent pre-treatment and infection status as following; sample group - pre-treatment - infection KO_MK_*hr - mock - mock KO_WNV_*hr - mock - WMV WT_IL1b_*hr - IL-1b - mock WT_MK_*hr - mock - mock WT_WNV_*hr - mock - WMV The *hr represents the time after infection.