The indistinguishable disease phenotypes of Tlr2/13–/– and Tlr2/4/13–/– mice, along with their similarity to the Myd88–/– disease phenotype, suggest that TLR2 and -13 are the primary drivers of innate immune activation during pneumococcal infection of the murine CNS. The gene discussed is TLR2; the disease is pneumococcal infection.