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Updated: Aug 15, 2026

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Regulation of Streptococcus pneumoniae distribution by Toll-like receptor 2 in vivo
Hakim Echchannaoui1, Philipp Bachmann, Maryse Letiembre
1Division of Infectious Diseases, Department of Research, University Hospital, Hebelstrasse 20, CH-4031 Basel, Switzerland.
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.
Insights
Toll-like receptor 2 (TLR2) helps reduce bacterial load in Gram-positive infections. While not affecting distribution, TLR2 may enhance bacterial clearance by influencing adherence and uptake in brain plexus epithelial cells.
Area of Science:
- Immunology
- Microbiology
- Neuroscience
Background:
- Toll-like receptor 2 (TLR2) and MyD88 are crucial for reducing Gram-positive bacterial infections.
- Their precise antibacterial mechanisms remain largely unknown.
- Previous studies showed increased pathogen burden in TLR2-/- and MyD88-/- mice.
Purpose of the Study:
- To investigate the role of TLR2 in the interaction between Streptococcus pneumoniae and phagocytes in the brain.
- To compare bacterial distribution and localization in wild-type (wt) and TLR2-/- mice during meningitis.
Main Methods:
- Confocal microscopy was used to visualize green fluorescent protein-transformed encapsulated S. pneumoniae (C5017) in the brains of wt and TLR2-/- mice.
- Bacterial colony-forming units (CFUs) were quantified.
- Immunohistochemistry identified specific cell types, including GLT1v+ plexus choroideus epithelial cells, Gr-1+ granulocytes, F4/80+ macrophages, Iba1+ microglia, GFAP+ astrocytes, Meca-31+ endothelial cells, and Neun+ neurons.
Main Results:
- Bacterial distribution (meninges and ventricles) was similar in both wt and TLR2-/- mice.
- Bacteria were more abundant in ventricles and associated with TLR2-/- plexus choroideus epithelial cells compared to wt.
- S. pneumoniae were found in granulocytes but not in macrophages, microglia, astrocytes, endothelial cells, or neurons.
Conclusions:
- TLR2 does not alter the overall distribution of S. pneumoniae in the brain.
- TLR2 may play a role in antibacterial defense by modulating bacterial adherence and uptake in plexus epithelia.
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