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Status |
Public on Dec 18, 2009 |
Title |
Gene expression in the Schistosoma japonicum infected spleen |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
Determining the molecular events induced in the spleen during schistosome infection is an essential step in better understanding the immunopathogenesis of schistosomiasis and the mechanisms by which schistosomes modulate the host immune response. The present study defines the transcriptional and cellular events occurring in the murine spleen during the progression of Schistosoma japonicum infection. Additionally, we compared and contrasted these results with those we have previously reported for the liver. Microarray analysis combined with flow cytometry and histochemistry demonstrated that transcriptional changes occurring in the spleen were closely related to changes in cellular composition. Additionally, the presence of alternatively activated macrophages, as indicated by up-regulation of Chi3l3 and Chi3l4 and expansion of F4/80+ macrophages, together with enhanced expression of the immunoregulatory genes ANXA1 and CAMP suggests the spleen may be an important site for the control of S. japonicum-induced immune responses. The most striking difference between the transcriptional profiles of the infected liver and spleen was the contrasting expression of chemokines and cell adhesion molecules. Lymphocyte chemokines including the homeostatic chemokines, CXCL13, CCL19 and CCL21, were significantly down-regulated in the spleen but up-regulated in the liver. Eosinophil (CCL11, CCL24), neutrophil (CXCL1) and monocyte (CXCL14, CCL12) chemokines and the cell adhesion molecules VCAM1, NCAM1, PECAM1 were up-regulated in the liver but unchanged in the spleen. Chemokines up-regulated in both organs were expressed at significantly higher levels in the liver. Co-ordinated expression of these genes probably contributes to the development of a chemotactic signalling gradient that promotes recruitment of effector cells to the liver, thereby facilitating the development of hepatic granulomas and fibrosis. Together these data provide, for the first time, a comprehensive overview of the molecular events occurring in the spleen during schistosomiasis and will substantially further our understanding of the local and systemic mechanisms driving the immunopathogenesis of this disease.
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Overall design |
The gene expression profile of the murine spleen were examined at 4, 6 and 7 weeks post infection with Schistosoma japonicum in comparison to that of uninfected controls. Microarray analysis was performed on pooled RNA from 4 mice per group. Two technical replicates were performed for each cRNA sample.
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Contributor(s) |
Burke ML, McManus DP, Ramm GA, Duke M, Li Y, Jones MK, Gobert GN |
Citation(s) |
20502518 |
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Submission date |
Dec 17, 2009 |
Last update date |
Mar 21, 2012 |
Contact name |
Melissa Louise Burke |
E-mail(s) |
melissa.burke@qimr.edu.au
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Organization name |
Queensland Institute of Medical Research
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Department |
Division of Infectious Diseases and Immunology
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Lab |
Molecular Parasitology
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Street address |
300 Herston Road
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City |
Herston |
State/province |
QLD |
ZIP/Postal code |
4006 |
Country |
Australia |
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Platforms (1) |
GPL6481 |
Illumina mouse-6 v1.1 expression beadchip [Array_Address_Id version] |
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Samples (8)
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Relations |
BioProject |
PRJNA122239 |