In this report, we show that, after stimulation with poly(I:C) or malaria parasite-infected red blood cells (iRBCs), FOSL1 was “translocated” from the nucleus to the cytoplasm, where it interacted with TRAF3 and TRIF to reduce IRF3 phosphorylation and IFN-I signaling. Here, FOSL1 is linked to malaria.