Transcriptomics

Dataset Information

0

Hsp70 and a Novel Axis of Type 1 Interferon-Dependent Antiviral Immunity in the Measles Virus-Infected Brain


ABSTRACT: The major inducible 70 kDa heat shock protein (hsp70) is host protective in a mouse model of measles virus (MeV) brain infection. Transgenic constitutive expression of hsp70 in neurons, the primary target of MeV infection, abrogates neurovirulence in neonatal H-2d congenic C57BL/6 mice. A significant level of protection is retained after depletion of T lymphocytes, implicating innate immune mechanisms. Focus of the present work was to elucidate the basis for hsp70-dependent innate immunity using this model. Transcriptome analysis of brains from transgenic (TG) and non-transgenic (NT) mice 5 days after infection identified type 1 interferon (IFN) signaling and macrophage activation/antigen presentation as the main differences linked to survival. The pivotal role for type 1 IFN in hsp70-mediated protection was demonstrated in mice with a genetically disrupted type 1 IFN receptor (IFNAR-/-), where IFNAR-/- eliminated the difference in survival between TG and NT mice. Brain macrophages, not neurons, are the predominant source of type 1 IFN in the virus-infected brain, and in vitro studies provided a mechanistic basis by which MeV-infected neurons can induce IFN-β in uninfected microglia in an hsp70-dependent manner. MeV infection induced extracellular release of hsp70 from mouse neuronal cells that constitutively express hsp70, and extracellular hsp70 induced IFN-β transcription in mouse microglial cells through Toll-like receptors 2 and 4. Collectively, results support a novel axis of type 1 IFN-dependent antiviral immunity in the virus-infected brain that is driven by hsp70.

ORGANISM(S): Mus musculus

PROVIDER: GSE42264 | GEO | 2012/11/14

SECONDARY ACCESSION(S): PRJNA179489

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2012-11-14 | E-GEOD-42264 | biostudies-arrayexpress
2017-12-14 | GSE100873 | GEO
2017-12-14 | GSE102179 | GEO
2017-12-31 | GSE98423 | GEO
2023-11-22 | GSE195828 | GEO
2018-12-28 | GSE124399 | GEO
2016-12-01 | GSE89476 | GEO
2009-01-14 | E-GEOD-13522 | biostudies-arrayexpress
2020-04-09 | GSE142707 | GEO
2020-04-09 | GSE142708 | GEO