Toll-like receptors in brain abscess.
Brain abscesses arise from a localized parenchymal infection, typically elicited by pyogenic bacteria such as Staphylococcus aureus. Despite improvements in detection and treatment strategies, brain abscesses continue to occur, with an increased prevalence in developing countries and immune-compromised patients. Adding to the seriousness of these infections is the recent emergence of antibiotic-resistant strains of bacteria, which are becoming more commonly associated with brain abscesses. Recent studies using a mouse experimental brain abscess model have revealed a complex role for Toll-like receptors (TLRs) in disease pathogenesis. Interestingly, TLR2 has limited impact on the innate immune response during the acute stage of brain abscess formation induced by S. aureus but influences adaptive immunity. In contrast, mice deficient in MyD88, a central adapter molecule for the majority of TLRs in addition to the IL-1R and IL-18R, demonstrate severe defects in innate immunity coupled with exaggerated tissue destruction. It is envisioned that understanding the roles for TLRs in both resident CNS glia as well as infiltrating immune cells will provide insights into how the immune response to bacterial infection can be tailored to achieve effective pathogen destruction without inducing excessive bystander damage of surrounding noninfected brain parenchyma. A discussion of recent findings in this field is presented along with outstanding questions and the concept of a pathogen-necrosis-autoantigen triad for the amplification of TLR signaling is introduced.
Esen
Nilufer
N
Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
Kielian
Tammy
T
D000818:Animals; D001922:Brain Abscess / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology*
D051195:Toll-Like Receptor 2
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