Toll-like receptors in bacterial meningitis

Abstract

Bacterial meningitis is still an important infectious disease with a high morbidity and mortality rate. Bacterial infection of the cerebrospinal fluid (CSF) space causes a powerful inflammatory reaction that is largely responsibly for meningitis-induced tissue damage and adverse outcome of the disease. In a landmark series of experiments in the mid-1980s, cell wall components including lipooligosaccharides and lipoteichoic acid were indicated to be the key bacterial elements that can trigger the host inflammatory response in the CSF. Ten years ago, the discovery of Toll-like receptor proteins (TLRs) that allow the detection of microbial components and initiate the host immune response opened up new horizons in research on the pathophysiology of meningitis. Cell culture approaches provided the first evidence for a crucial role of TLRs in sensing meningeal pathogens including Streptococcus pneumoniae, Neisseria meningitidis, Streptococcus agalactiae, and Listeria monocytogenes. Subsequently, studies in mice with single or combined deficiencies in TLRs demonstrated that TLR activation is a key event in meningeal inflammation and, even more interestingly, a pivotal factor for meningitis-associated tissue damage. A detailed understanding of the mechanisms of host-pathogen interactions in the CSF space may generate new opportunities for specific treatment strategies for bacterial meningitis.