chapter  9
18 Pages

Role of Toll-Like Receptor Signaling in Central Nervous System Infections ............................................................................. Tammy Kielian

Acknowledgments .................................................................................................. 155 References .............................................................................................................. 155

Bacterial infections can be generally subdivided into two categories based on the anatomical location of lesions. Bacterial meningitis, as the name implies, involves infection of the subarachnoid space and can be caused by a wide array of organisms. Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae are among the leading etiologic agents of community-acquired meningitis in humans.1,2 Despite advances made in vaccination and treatment strategies, bacterial meningitis remains associated with a significant mortality rate and incidence of neurological sequelae, particularly in very young and elderly patients. Long-term effects resulting from meningitis include hearing loss, hydrocephalus, and sequelae associated with parenchymal damage including memory loss, cerebral palsy, learning disabilities, and seizures.3,4 Bacterial meningitis elicits a complex myriad of pathophysiological changes, many of which have been attributed to an excessive host antibacterial immune response. For example, besides the direct damage induced by pathogens,

the host antibacterial response elicited during the acute phase of bacterial meningitis can be detrimental to neurons and other glia in the CNS due to the toxic effects of cytokines, chemokines, proteolytic enzymes, and oxidants produced locally at the site of infection.1,2,5,6 Work by other laboratories has implicated TLR2 as an important sensor of bacterial infection in Streptococcus pneumoniae meningitis leading to the subsequent release of proinflammatory mediators that have been implicated in host tissue damage.7,8 An additional report has indicated that MyD88, one of the major adaptor proteins utilized for transducing TLR activation signals, also impacts the host response to meningitis.9