Toll-like receptors: insights into their possible role in the pathogenesis of lyme neuroborreliosis.
Lyme neuroborreliosis is likely caused by inflammatory effects of the tick-borne spirochete Borrelia burgdorferi on the nervous system. Microglia, the resident macrophage cells within the central nervous system (CNS), are important in initiating an immune response to microbial products. In addition, astrocytes, the major CNS glial cell type, also can contribute to brain inflammation. TLRs (Toll-like receptors) are used by glial cells to recognize pathogen-associated molecular patterns (PAMPs), mediate innate responses, and initiate an acquired immune response. Here we hypothesize that because of their PAMP specificities, TLR1, -2, -5, and -9 may be involved in the pathogenesis of Lyme neuroborreliosis. Previous reports have shown that the rhesus monkey is the only animal model to exhibit signs of Lyme neuroborreliosis. Therefore, we used primary cultures of rhesus astrocytes and microglia to determine the role of TLRs in mediating proinflammatory responses to B. burgdorferi. The results indicate that microglia and astrocytes respond to B. burgdorferi through TLR1/2 and TLR5. In addition, we observed that phagocytosis of B. burgdorferi by microglia enhances not only the expression of TLR1, -2, and -5, but also that of TLR4. Taken together, our data provide proof of the concept that astrocyte and microglial TLR1, -2, and -5 are involved in the in vivo response of primate glial cells to B. burgdorferi. The proinflammatory molecules elicited by these TLR-mediated responses could be a significant factor in the pathogenesis of Lyme neuroborreliosis.
Bernardino
Andrea L F
AL
Division of Bacteriology and Parasitology, Tulane National Primate Research Center, Tulane University, Covington, Louisiana 70433, USA.
Myers
Tereance A
TA
Alvarez
Xavier
X
Hasegawa
Atsuhiko
A
Philipp
Mario T
MT
D000818:Animals; D001253:Astrocytes / Q000382:microbiology; D015153:Blotting, Western; D025065:Borrelia burgdorferi / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression; D020852:Lyme Neuroborreliosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D008253:Macaca mulatta; D017628:Microglia / Q000382:microbiology; D010587:Phagocytosis; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000276:immunology*
D016207:Cytokines; D012333:RNA, Messenger; D051193:Toll-Like Receptors