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The core mouse response to infection by neospora caninum defined by gene set enrichment analyses.

ABSTRACT: In this study, the BALB/c and Qs mouse responses to infection by the parasite Neospora caninum were investigated in order to identify host response mechanisms. Investigation was done using gene set (enrichment) analyses of microarray data. GSEA, MANOVA, Romer, subGSE and SAM-GS were used to study the contrasts Neospora strain type, Mouse type (BALB/c and Qs) and time post infection (6 hours post infection and 10 days post infection). The analyses show that the major signal in the core mouse response to infection is from time post infection and can be defined by gene ontology terms Protein Kinase Activity, Cell Proliferation and Transcription Initiation. Several terms linked to signaling, morphogenesis, response and fat metabolism were also identified. At 10 days post infection, genes associated with fatty acid metabolism were identified as up regulated in expression. The value of gene set (enrichment) analyses in the analysis of microarray data is discussed.

SUBMITTER: Ellis J

PROVIDER: S-EPMC3448498 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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The core mouse response to infection by neospora caninum defined by gene set enrichment analyses.

Ellis John J Goodswen Stephen S Kennedy Paul J PJ Bush Stephen S

Bioinformatics and biology insights 20120903

In this study, the BALB/c and Qs mouse responses to infection by the parasite Neospora caninum were investigated in order to identify host response mechanisms. Investigation was done using gene set (enrichment) analyses of microarray data. GSEA, MANOVA, Romer, subGSE and SAM-GS were used to study the contrasts Neospora strain type, Mouse type (BALB/c and Qs) and time post infection (6 hours post infection and 10 days post infection). The analyses show that the major signal in the core mouse resp ...[more]

PMID: 23012496

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Project description:BackgroundNeospora caninum is an intracellular parasite that causes significant economic losses in cattle industry. Understanding the host resistance mechanisms in the innate immune response to neosporosis could facilitate the exploration of approaches for controlling N. caninum infection. The NLR inflammasome is a multiprotein platform in the cell cytoplasm and plays critical roles in the host response against microbes.MethodsNeospora caninum-infected wild-type (WT) macrophages and Nlrp3 -/- macrophages, and inhibitory approaches were used to investigate inflammasome activation and its role in N. caninum infection. Inflammasome RT Profiler PCR Arrays were used to identify the primary genes involved in N. caninum infection. The expression of the sensor protein NLRP3, processing of caspase-1, secretion of IL-1β and cell death were detected. Neospora caninum replication in macrophages was also assessed.ResultsMany NLR molecules participated in the recognition of N. caninum, especially the sensor protein NLRP3, and further study revealed that the NLRP3 distribution became punctate in the cell cytoplasm, which facilitated inflammasome activation. Inflammasome activation-mediated caspase-1 processing and IL-1β cleavage in response to N. caninum infection were observed and were correlated with the time of infection and number of infecting parasites. LDH-related cell death was also observed, and this death was regarded as beneficial for the clearance of N. caninum. Treatment of N. caninum-infected macrophages with caspase-1, pan-caspase and NLRP3 inhibitors led to the impaired release of active IL-1β and a failure to restrict parasite replication. And Neospora caninum infected peritoneal macrophages from Nlrp3-deficient mice displayed greatly decreased release of active IL-1β and the failure of caspase-1 cleavage.ConclusionsThe NLRP3 inflammasome can be activated in N. caninum-infected macrophages, and plays a protective role in the host response to control N. caninum.

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The core mouse response to infection by neospora caninum defined by gene set enrichment analyses.

Publications

The core mouse response to infection by neospora caninum defined by gene set enrichment analyses.

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