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Title: Adjuvant induced attenuation of excessive inflammation in mice infected with pandemic H1N1 (H1N1pdm) virus      
dateReleased:
09-10-2014
description:
The reassorted human 2009 pandemic H1N1 (H1N1pdm) virus infected millions of people and caused thousands of deaths with associated immunopathology. Traditional immunosuppressants have limited capabilities in controlling inflammatory responses associated with severe influenza infections. A new therapeutic strategy, therefore, must be developed. We evaluated several adjuvants including toll-like receptor (TLR) agonists, TLR independent adjuvants and Complete Freund’s adjuvant (CFA) for limiting severe H1N1pdm infection outcomes in a mouse model. In contrast to the TLR agonists and TLR independent adjuvants, CFA which contains multiple pattern recognition receptor (PRR) agonists significantly restrained pro-inflammatory responses and promoted survival in mice from lethal H1N1pdm infection. CFA reduced expression of the plamacytoid dendritic cell (pDC) markers and interferon alpha (IFN-α) after infection, whereas it elevated the T regulatory (Treg) cell suppressive molecules galectin-1 and CTLA-4 expression. Consequently, Th1 cell differentiation and CD8+ effector T cell responses were diminished via downregulated myeloid DC (mDC) costimulation. Furthermore, CTLA-4 expressing Treg cells were dramatically increased when the CFA primed splenocytes were restimulated with its stimuli-killed mycobacterium tuberculosis (M. TB). The elevated CTLA-4 on Treg cells led to reduced CD86 expressing pDCs/mDCs and less CD4+ effector T cells. Overall, our study highlights that the stimuli of innate immunity potentially controls overactive host immune responses in certain situations, and the uncovered mechanism(s) sheds light on the development of anti-influenza therapies. C57B6/J Mice were treated with CFA at day -2 and day 2 post H1N1pdm infection. Weight loss and lethality were monitored post infection. At day 3 and day 5 lung tissues were collected for RNA extraction and expression array analysis.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-41088
refinement:
raw
alternateIdentifiers:
41088
keywords:
functional genomics
dateModified:
09-13-2014
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-MEXP-1175
name:
Illumina MouseWG-6 v2.0 Expression BeadChip
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-41088/E-GEOD-41088.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-41088/E-GEOD-41088.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE41088
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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