Type I Interferon Regulates the Dynamics of Innate Myeloid Sentinel Cells During Persistent Viral Infection (169.7)
| Autor: | Debasis Nayak, Kory Johnson, Sara Heydari, Theodore Roth, Bernd Zynselmeyer, Dorian McGavern |
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| Rok vydání: | 2012 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 188:169.7-169.7 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Viral infections of brain usually trigger inflammatory responses that give rise to a wide range of pathological outcomes. To gain novel insights into how the brain responds to a virus as it establishes persistence, we utilized genomic and two-photon imaging approaches to study a pure innate immune response to a lymphocytic choriomeningitis virus (LCMV) infection. This was accomplished by monitoring temporal gene expression patterns and myeloid cells dynamics in the brain of CX3CR1-GFP mice lacking LCMV-specific T cells. Within the first two weeks of infection, brain resident myeloid cells were highly activated and responded directly by sequestering DsRed-labeled viral antigen. At the genomic level, this triggered massive changes in gene expression that were attenuated over time (likely due to inhibition by viral nucleoprotein) and were all directly linked to type I interferon (IFN-I) signaling. Surprisingly, in the absence of IFN-I signaling, no genes were differentially expressed in the nervous system despite the presence of persistent virus. In addition, two-photon imaging studies revealed that IFN-I receptor deficient innate immune sentinels were completely unresponsive to the establishment of a persistent viral infection. These data demonstrate that IFN-I drives all innate immune activity in the brain following LCMV infection, and deficiency in IFN-I signaling renders LCMV invisible in its murine host. |
| Databáze: | OpenAIRE |
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