Immunobiology 210 (2005) 229–236 Regulation of Streptococcus pneumoniae distribution by Toll-like receptor 2 in vivo Hakim Echchannaoui a , Philipp Bachmann a , Maryse Letiembre a , Manuel Espinosa b , Regine Landmann a,à a Division of Infectious Diseases, Department of Research, University Hospital, Hebelstrasse 20, CH-4031 Basel, Switzerland b Centro de Investigaciones Biolo´gicas, Consejo Superior de Investigaciones Cientı´ficas, Ramiro de Maeztu, 9, E-28040 Madrid, Spain Received 4 April 2005; accepted 23 May 2005 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. r 2005 Elsevier GmbH. All rights reserved. Keywords: Distribution; Meningitis; Streptococcus pneumoniae; TLR2 Introduction Toll-like receptor 2 (TLR2)- and MyD88-dependent pathways are central components of innate host defense mechanisms against Gram-positive bacteria. Murine models show, that TLR2 and the adaptor molecule MyD88 confer resistance to infection with the intracel- lular microorganisms Mycobacterium tuberculosis and Listeria monocytogenes, but also to infection with extracellular pathogens including staphylococci and ARTICLE IN PRESS www.elsevier.de/imbio 0171-2985/$ - see front matter r 2005 Elsevier GmbH. All rights reserved. doi:10.1016/j.imbio.2005.05.017 Abbreviations: CCD, charge-coupled device; CFU, colony-forming units; CSF, cerebrospinal fluid; GBS, Group B streptococci; GFP, green fluorescent protein; MFI, mean fluorescence intensity; S., Streptococcus; TLR2, Toll-like receptor 2; wt, C57BL/6 wild type à Corresponding author. Tel.: +41 61 265 23 25; fax: +41 61 265 23 50. E-mail address: regine.landmann@unibas.ch (R. Landmann).