Innate immunity to pneumococcal infection of the central nervous system depends on toll-like receptor (TLR) 2 and TLR4.

BACKGROUND: Recent studies have suggested that, in addition to Toll-like receptor (TLR) 2, other pattern recognition receptors mediate activation of the immune response after infection of the central nervous system (CNS) with Streptococcus pneumoniae (SP). METHODS: Using a mouse meningitis model, we investigated the influence of TLR4 single deficiency (TLR4(-/-)), TLR2/TLR4 double deficiency (TLR2/4(-/-)), and TLR2/TLR4/TLR9 triple deficiency (TLR2/4/9(-/-)) on the immune response of the CNS to SP infection. To identify the cell populations that mediate the responses to SP, we generated TLR2/4(-/-)-wild-type (wt) bone marrow (BM) chimeras. RESULTS: Compared with infected wt mice, infected TLR2/4(-/-) and TLR2/4/9(-/-) mice had similar reductions in brain cytokine levels, pleocytosis, and cerebral pathologic findings, whereas no such effect was noted in infected TLR4(-/-) mice. The attenuated immune response was paralleled by an impaired host defense that resulted in worsening of disease. Analysis of the chimeric mice after infection showed that mere TLR2/4 deficiency, either of radioresistant cells or of transplanted BM-derived cells, was sufficient to mount a substantial cerebral immune response, such as that noted in wt mice. CONCLUSION: In murine SP meningitis, TLR2 and TLR4 expressed on radioresistant and transplanted BM-derived cells were major cellular sensors of invading SP inducing inflammatory responses.     «

BACKGROUND: Recent studies have suggested that, in addition to Toll-like receptor (TLR) 2, other pattern recognition receptors mediate activation of the immune response after infection of the central nervous system (CNS) with Streptococcus pneumoniae (SP). METHODS: Using a mouse meningitis model, we investigated the influence of TLR4 single deficiency (TLR4(-/-)), TLR2/TLR4 double deficiency (TLR2/4(-/-)), and TLR2/TLR4/TLR9 triple deficiency (TLR2/4/9(-/-)) on the immune response of the CNS to...     »