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Series GSE7767 Query DataSets for GSE7767
Status Public on Jul 15, 2007
Title Differential transcription of ip Chlamydia infected C57BL6J and DBA2J mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary C57BL/6J mice were 105-fold more resistant to Chlamydia psittaci infection than DBA/2J mice by LD100 determinations. Linkage analysis using BXD recombinant inbred strains revealed a single effector locus at a 1.5 Mbp region on chromosome 11 encoding a cluster of three p47GTPases (Irgb10, Igtp, and Iigp2). Western blots of infected tissue showed that Irgb10 was elevated in resistant mice and one of the two possible Iigp2 protein isoforms was preferentially expressed in susceptible mice. The BXD39 strain, susceptible at Irgb10 and resistant at Iigp2, had an intermediate phenotype, implicating the non-redundant role of these p47GTPases. C57BL/6J and DBA/2J exhibited a difference in IFNg dependent chlamydial control, which was reversible by Iigp2 siRNA knockdown. Microarrays of infected peritoneal lavage revealed >10 fold up regulation of neutrophil recruiting chemokines in susceptible mice and >100 fold increase in macrophage differentiation genes in resistant mice, indicating that susceptibility pattern involves stimulation of different inflammatory cell recruiting pathways. Massive neutrophil recruitment was seen in susceptible mice by histology and flow cytometry, and neutrophil chemokine receptor (CXCR2) knockout mice on a susceptible background survived lethal challenge confirming that neutrophil recruitment was required for susceptibility. Congenic Igtp knockout mice also susceptible at Irgb10 and Iigp2 on a resistant background recruited neutrophils and succumbed to infection. We conclude that Irgb10 and Iigp2 act together to confer differential susceptibility against murine chlamydial infection. Results indicate that these p47GTPases have cell autonomous effects, which results in vastly different inflammatory stimulation leading to either recovery or death.
Keywords: Comparative disease state analysis
 
Overall design C57BL/6J and DBA2J mice (4 mice each) were infected I.p. with 10E4 IFU of Chlamydia psittaci then peritoneal lavage was collected on day 3 post infection. Cells were centrifuged then treated with Trizol for total RNA extraction.
 
Contributor(s) Miyairi I, Byrne GI, Belland RJ, Lu L, Williams RW, Rose L, Qu Y
Citation(s) 17641048
Submission date May 09, 2007
Last update date Feb 11, 2019
Contact name Lorne A Rose
E-mail(s) lrose4@utmem.edu
Phone 901-448-4459
Organization name University of Tennessee
Department Molecular Sciences
Street address 854 Madision Ave
City Memphis
State/province TN
ZIP/Postal code 38163
Country USA
 
Platforms (1)
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (6)
GSM188240 C57BL6J mice infected peritoneal lavage day 3pi, biological repeat 2
GSM188241 C57BL6J mice infected peritoneal lavage day 3pi, biological repeat 3
GSM188242 C57BL6J mice infected peritoneal lavage day 3pi, biological repeat 5
Relations
BioProject PRJNA99783

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Supplementary file Size Download File type/resource
GSE7767_RAW.tar 23.6 Mb (http)(custom) TAR (of CEL, EXP)
Raw data provided as supplementary file

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