We found that animals deficient in either TLR3 (Tlr3−/−) or Cardif (Cardif−/−) had a trend towards improved bacterial clearance following poly I:C-pre-exposure, whereas poly I:C exposed Cardif/Tlr3 double knockout (Cardif−/−/Tlr3−/−) animals had significantly enhanced clearance of secondary bacterial infection that was comparable to saline-exposed animals. Here, TLR3 is linked to bacterial infectious disease.