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Matthias Klein, Bianca Obermaier, Barbara Angele, Hans-Walter Pfister, Hermann Wagner, Uwe Koedel, Carsten J. Kirschning, Innate Immunity to Pneumococcal Infection of the Central Nervous System Depends on Toll-Like Receptor (TLR) 2 and TLR4, The Journal of Infectious Diseases, Volume 198, Issue 7, 1 October 2008, Pages 1028–1036, https://doi.org/10.1086/591626
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Abstract
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.
Conclusions. 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.
