Lack of Toll-like receptor 2 results in higher mortality of bacterial meningitis by impaired host resistance.

Abstract

Bacterial meningitis is - despite therapeutical progress during the last decades - still characterized by high mortality and severe permanent neurogical sequelae. The brain is protected from penetrating pathogens by both the blood-brain barrier and the innate immune system. Invading pathogens are recognized by so-called pattern recognition receptors including the Toll-like receptors (TLR) which are expressed by glial immune cells in the central nervous system. Among these, TLR2 is responsible for the detection of Gram-positive bacteria such as the meningitis-causing pathogen Streptococcus pneumoniae. Here, we used TLR2-deficient mice to investigate the effects on mortality, bacterial growth and inflammation in a mouse model of pneumococcal meningitis. Our results revealed a significantly increased mortality rate and higher bacterial burden in TLR2-deficient mice with pneumococcal meningitis. Furthermore, infected TLR2-deficient mice suffered from a significantly increased pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and Chemokine (C-C motif) ligand 2 (CCL2) or CCL3 chemokine expression and decreased expression of anti-inflammatory cytokines and antimicrobial peptides. In contrast, glial cell activation assessed by glial cell marker expression was comparable to wildtype mice. Taken together, the results suggest that TLR2 is essential for an efficient immune response against Streptococcus pneumoniae meningitis since lack of the receptor led to a worse outcome by higher mortality due to increased bacterial burden, weakened innate immune response and reduced expression of antimicrobial peptides.

• Authors: Martin Böhland, Eugenia Kress, Matthias B Stope, Thomas Pufe, Simone C Tauber, Lars-Ove Brandenburg
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 299 Pg. 90-97 (10 15 2016) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 27725130 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Tlr2 protein, mouse
• Toll-Like Receptor 2

Topics

• Animals
• Immunity, Innate (physiology)
• Meningitis, Pneumococcal (immunology, metabolism, mortality)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mortality (trends)
• Neuroglia (immunology, metabolism)
• Toll-Like Receptor 2 (deficiency, immunology)