| First Author | Lehnardt S | Year | 2007 |
| Journal | J Immunol | Volume | 179 |
| Issue | 9 | Pages | 6134-43 |
| PubMed ID | 17947688 | Mgi Jnum | J:152996 |
| Mgi Id | MGI:4360584 | Doi | 10.4049/jimmunol.179.9.6134 |
| Citation | Lehnardt S, et al. (2007) TLR2 and caspase-8 are essential for group B Streptococcus-induced apoptosis in microglia. J Immunol 179(9):6134-43 |
| abstractText | Microglia, the resident innate immune cells of the CNS, detect invading pathogens via various receptors, including the TLR. Microglia are involved in a number of neurodegenerative diseases in which their activation may be detrimental to neurons. It is largely unknown how this potentially deleterious action can be countered on a cellular level. We previously found that the interaction of TLR2 with group B Streptococcus (GBS), the most important pathogen in neonatal bacterial meningitis, activates microglia that in turn generate neurotoxic NO. We report in this study that GBS not only activates microglia, but also induces apoptosis in these cells via TLR2 and the TLR-adaptor molecule MyD88. Soluble toxic mediators, such as NO, are not responsible for this form of cell death. Instead, interaction of GBS with TLR2 results in formation and activation of caspase-8, a process that involves the transcription factor family Ets. Whereas caspase-8 plays an essential role in GBS-induced microglial apoptosis, caspase-3 is dispensable in this context. We suggest that TLR2- and caspase-8-mediated microglial apoptosis constitutes an autoregulatory mechanism that limits GBS-induced overactivation of the innate immune system in the CNS. |
