| First Author | Henn A | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 5 | Pages | 3237-47 |
| PubMed ID | 21282508 | Mgi Jnum | J:169379 |
| Mgi Id | MGI:4940911 | Doi | 10.4049/jimmunol.1002787 |
| Citation | Henn A, et al. (2011) TLR2 Hypersensitivity of Astrocytes as Functional Consequence of Previous Inflammatory Episodes. J Immunol 186(5):3237-47 |
| abstractText | Precedent inflammatory episodes may drastically modify the function and reactivity of cells. We investigated whether priming of astrocytes by microglia-derived cytokines alters their subsequent reaction to pathogen-associated danger signals not recognized in the quiescent state. Resting primary murine astrocytes expressed little TLR2, and neither the TLR2/6 ligand fibroblast-stimulating lipopeptide-1 (FSL1) nor the TLR1/2 ligand Pam(3)CysSK(4) (P3C) triggered NF-kappaB translocation or IL-6 release. We made use of single-cell detection of NF-kappaB translocation as easily detectable and sharply regulated upstream indicator of an inflammatory response or of c-Jun phosphorylation to measure restimulation events in astrocytes under varying conditions. Cells prestimulated with IL-1beta, with a TLR3 ligand, with a complete cytokine mix consisting of TNF-alpha, IL-1beta, and IFN-gamma, or with media conditioned by activated microglia responded strongly to FSL1 or P3C stimulation, whereas the sensitivity of the NF-kappaB response to other pattern recognition receptors was unchanged. This sensitization to TLR2 ligands was associated with an initial upregulation of TLR2, displayed a 'memory' window of several days, and was largely independent of the length of prestimulation. The altered signaling led to altered function, as FSL1 or P3C triggered the release of IL-6, CCL-20, and CXCL-2 in primed cells, but not in resting astrocytes. These data confirmed the hypothesis that astrocytes exposed to activated microglia assume a different functional phenotype involving longer term TLR2 responsiveness, even after the initial stimulation by inflammatory mediators has ended. |
