By using specific TLR2 and TLR4-genetically deficient cell lines, it is reasonable to hypothesize an intracellular TLR2 signaling pathway, a scenario described in a recently reported study, showing that Staphylococcus aureus infection of human monocytes activates a TLR2-dependent endosomal signaling pathway, leading to type I IFN induction in a TRIF-independent manner [25]. The gene discussed is TLR4; the disease is staphylococcus aureus infection.