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By D.J. Trindle (Editor)

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J Infect Dis 166:650–652 Toll-Like Receptors in Bacterial Meningitis 35 Braun JS, Sublett JE, Freyer D, Mitchell TJ, Cleveland JL, Tuomanen EI, Weber JR (2002) Pneumococcal pneumolysin and H2O2 mediate brain cell apoptosis during meningitis. J Clin Invest 109:19–27 Bsibsi M, Ravid R, Gveric D, van Noort JM (2002) Broad expression of Toll-like receptors in the human central nervous system. J Neuropathol Exp Neurol 61:1013–1021 De Luigi A, Terreni L, Sironi M, De Simoni MG (1998) The sympathetic nervous system tonically inhibits peripheral interleukin-1beta and interleukin-6 induction by central lipopolysaccharide.

Cell 86:973–983 Letiembre M, Echchannaoui H, Bachmann P, Ferracin F, Nieto C, Espinosa M, Landmann R (2005) Toll-like receptor 2 deficiency delays pneumococcal phagocytosis and impairs oxidative killing by granulocytes. Infect Immun 73:8397–8401 Letiembre M, Hao W, Liu Y, Walter S, Mihaljevic I, Rivest S, Hartmann T, Fassbender K (2007) Innate immune receptor expression in normal brain aging. Neuroscience 146:248–254 Magnusson M, Tobes R, Sancho J, Pareja E (2007) Cutting edge: natural DNA repetitive extragenic sequences from gram-negative pathogens strongly stimulate TLR9.

However, in vivo studies using mice with targeted deletions of individual TLRs (and other PRRs) are needed to assess whether these results can be extrapolated to in vivo models of bacterial meningitis. So far, the in vivo relevance of TLRs for mounting an inflammatory response to meningeal infection has been demonstrated only for S. pneumoniae, as outlined in the next section. 5 Role of TLRs in Pneumococcal Meningitis The first evidence for TLR involvement in pneumococcal meningitis was provided by Echchannaoui et al.

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