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.


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.
Klein
Matthias
M
Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Germany.
Obermaier
Bianca
B
Angele
Barbara
B
Pfister
Hans-Walter
HW
Wagner
Hermann
H
Koedel
Uwe
U
Kirschning
Carsten J
CJ
D000818:Animals; D001921:Brain / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D007113:Immunity, Innate; D008264:Macrophages / Q000276:immunology; D008586:Meningitis, Pneumococcal / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011836:Radiation Tolerance; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000302:isolation & purification; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000502:physiology*; D051217:Toll-Like Receptor 9 / Q000502:physiology
D016207:Cytokines; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9