Compared to MyD88 deficiency16,36, which profoundly suppresses host immunity against pathogens, double deficiency in TLR2 and TLR4 only modestly affected the immune response (as measured by immune mediator levels in the CSF) and mortality due to acute pneumococcal meningitis, likely due to a compensatory mechanism by another microbial pattern recognition system. Here, TLR4 is linked to pneumococcal meningitis.