title: Innate immunity to pneumococcal infection of the central nervous system depends on toll-like receptor (TLR) 2 and TLR4.
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.
authors.affiliation: Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Klein
authors.forename: Bianca
authors.initials: B
authors.lastname: Obermaier
authors.forename: Barbara
authors.initials: B
authors.lastname: Angele
authors.forename: Hans-Walter
authors.initials: HW
authors.lastname: Pfister
authors.forename: Hermann
authors.initials: H
authors.lastname: Wagner
authors.forename: Uwe
authors.initials: U
authors.lastname: Koedel
authors.forename: Carsten J
authors.initials: CJ
authors.lastname: Kirschning
mesh_terms: 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
chemical_list: 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