Despite the role of type I IFN in the pathogenesis of Chlamydia infection, it remains unresolved which PRRs are responsible for induction of the IFN response during infection with Chlamydia. In this work we demonstrate that C. pneumoniae induces expression of ISGs with a delayed kinetics relative to viruses, and that this is dependent on bacterial replication, innate immune recognition by intracellular nucleotide-sensing PRRs and signaling through TBK1/IKKε. Here, TBK1 is linked to chlamydia infectious disease.