title: Regulation of Streptococcus pneumoniae distribution by Toll-like receptor 2 in vivo.
abstract: The phagocyte pattern recognition receptor Toll-like receptor 2 (TLR2) and the multi-receptor adaptor MyD88 contribute to the reduction of bacterial load in infections with intra- and extra-cellular Gram-positive bacteria. Their mechanism of antibacterial action is mostly unresolved but evident in vivo by an increased pathogen burden in infected TLR2-/- and MyD88-/- compared to C57BL/6 wild type (wt) mice. We had previously observed higher bacterial numbers in brains of TLR2-/- than of wt mice with meningitis. Here we study bacteria-phagocyte interaction by comparing S. pneumoniae distribution and localization in wt and TLR2-/- brain by confocal microscopy using a green fluorescent protein-transformed encapsulated S. pneumoniae (C5017). Colony-forming units were similarly distributed in TLR2-/- and wt mice and exclusively localized in meninges and ventricles. Bacteria were more abundant in ventricles, in and around TLR2-/- than wt GLT1v+ plexus choroideus epithelial cells. S. pneumoniae were also found in and around Gr-1+ granulocytes, but never in F4/80+ macrophages, Iba1+ microglia, GFAP+ astrocytes, Meca-31+ endothelial cells or Neun+ neurons of either mouse strain. The results indicate that TLR2 does not change bacterial distribution, but may contribute to antibacterial defense by modulating S. pneumoniae adherence and uptake in plexus epithelia.
authors.affiliation: Division of Infectious Diseases, Department of Research, University Hospital, Hebelstrasse 20, CH-4031 Basel, Switzerland.
authors.forename: Hakim
authors.initials: H
authors.lastname: Echchannaoui
authors.forename: Philipp
authors.initials: P
authors.lastname: Bachmann
authors.forename: Maryse
authors.initials: M
authors.lastname: Letiembre
authors.forename: Manuel
authors.initials: M
authors.lastname: Espinosa
authors.forename: Regine
authors.initials: R
authors.lastname: Landmann
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology / Q000382:microbiology*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D008586:Meningitis, Pneumococcal / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D011971:Receptors, Immunologic / Q000172:deficiency / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000302:isolation & purification*; D051195:Toll-Like Receptor 2
chemical_list: D011971:Receptors, Immunologic; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D049452:Green Fluorescent Proteins