NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE51329 Query DataSets for GSE51329
Status Public on Jan 13, 2014
Title Strain-specific Innate Immune Signaling Pathways Determine Malaria Parasitemia Dynamics and Host Mortality
Organism Mus musculus
Experiment type Expression profiling by array
Summary Malaria infection triggers vigorous host immune responses; however, the parasite ligands, host receptors and the signaling pathways responsible for these reactions remain unknown or controversial. Malaria parasites primarily reside within red blood cells (RBCs), thereby hiding themselves from direct contact and recognition by host immune cells. Host responses to malaria infection are very different from those elicited by bacterial and viral infections and the host receptors recognizing parasite ligands have been elusive. Here we investigated mouse genome-wide transcriptional responses to infections with two strains of Plasmodium yoelii (N67 and N67C) and discovered differences in innate response pathways corresponding to strain-specific disease phenotypes. Using in vitro RNAi gene knockdown and knockout mice, we demonstrated that a strong IFN-I response triggered by RNA Polymerase III and melanoma differentiation-associated protein 5 (MDA5), not Toll-like receptors (TLRs), binding of parasite DNA/RNA contributed to a decline of parasitemia in N67-infected mice. We showed that conventional dendritic cells were the major sources of early IFN-I, and that surface expression of phosphatidylserine (PS) on infected RBC (iRBC) might promote their phagocytic uptake, leading to the release of parasite ligands and the IFN-I response in N67 infection. In contrast, an elevated inflammatory response mediated by CD14/TLR and p38 signaling played a role in disease severity and early host death in N67C-infected mice. In addition to identifying cytosolic DNA/RNA sensors and signaling pathways previously unrecognized in malaria infection, our study demonstrates the importance of parasite genetic backgrounds in malaria pathology and provides important information for studying human malaria pathogenesis.
 
Overall design Spleen RNA from mice, 4 days post infection with Plasmodium yoelii (strain N67 or N67C), or mock infection (N). Replicates from 6 individual mice per condition.
 
Contributor(s) Wu J, Tian L, Yu X, Pataradilokrat S, Li J, Yu W, Qi Y, Zeituni A, Nair SC, Crampton SP, Orandle MS, Bolland SM, Qi CF, Long CA, Myers TG, Coligan JE, Wang R, Su X
Citation(s) 24474800
Submission date Sep 30, 2013
Last update date Jun 14, 2018
Contact name Timothy G Myers
E-mail(s) niaid-mrf-geo@nih.gov
Organization name National Institute of Allergy and Infectious Diseases
Department Research Technologies Branch
Lab Genomic Technologies Section
Street address 50 South Drive, Room 5509
City Bethesda
State/province MD
ZIP/Postal code 20892-8005
Country USA
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (18)
GSM1242937 N1.1
GSM1242938 N67#1
GSM1242939 N67C#1
Relations
BioProject PRJNA222408

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE51329_RAW.tar 11.9 Mb (http)(custom) TAR (of TXT)
Raw data provided as supplementary file
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap