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Hsp70 and a novel axis of innate immunity in the virusinfected brain
Author(s) -
Oglesbee Michael,
Kim Mi Young,
Shu Yaoling,
Popovich Phil,
Niewiesk Stefan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.276.9
Subject(s) - innate immune system , biology , immunity , hsp70 , interferon , intrinsic immunity , microglia , microbiology and biotechnology , acquired immune system , transgene , immunology , virology , heat shock protein , immune system , inflammation , gene , genetics
The major inducible 70 kDa heat shock protein (hsp70) promotes viral gene expression and stimulates innate immunity when released from cells, but it is unknown how virus‐hsp70 interaction influences outcome of infection. This deficiency was addressed using the mouse model of measles virus (MeV) neuronal infection. Transgenic mice were made to constitutively express hsp70 in neurons (a primate‐pattern of hsp70 expression) and were completely protected from MeV brain infection, compared to 35% mortality in non‐transgenic infected controls. Complete protection required a viral transcriptional response to hsp70. Transcriptome analysis of infected brain showed that hsp70‐dependent innate immunity was associated with an interferon beta (IFN‐β) response that was not observed in non‐transgenic mice. Disruption of the type 1 interferon receptor confirmed that hsp70‐dependent protection was IFN‐dependent. In vitro data established a model for the hsp70‐dependent innate immunity. We showed that MeV‐infection stimulates exosomal release of hsp70 from neuronal cells, and that extracellular hsp70 stimulates production of IFN‐β in uninfected brain macrophages (microglial cells) in a Toll‐like receptor‐dependent manner. Hsp70 can be released by numerous viral pathogens, supporting the potential broad relevance of this novel pathway of innate immunity. Studies were supported by R01NS31693.