Unknown,Transcriptomics,Genomics,Proteomics

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Identification of molecular pathways in pigs with good and poor response to a porcine reproductive and respiratory syndrome (PRRS) genotype 1 vaccine strain.

ABSTRACT: The initial interaction of porcine reproductive and respiratory virus (PRRSV) with the immune system is of critical importance for immunological and clinical outcomes. PRRSV infection is associated with inefficient or aberrant immune responses: weak and delayed neutralizing antibody responses and erratic IFN-γ producing T-cells specific response. The lack of vaccine correlates capable of predicting protection has largely hampered the development of new efficacious PRRS vaccines. The objective of this study was to determine if systems biology (1) could be used to identify molecular pathways associated with “good” and “bad” PRRSV vaccine responders in terms of their intensity of IFN- γ secreting cell responses.

ORGANISM(S): Sus scrofa

SUBMITTER: Tahar AIT-ALI

PROVIDER: E-MTAB-3237 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The domestic pig (Sus scrofa) provides a large animal model for human innate immune responses and inflammation that is also economically important in its own right. Results: We demonstrate that macrophages can be harvested from 3 different compartments of the pig (lungs, blood and bone-marrow), cryopreserved and subsequently recovered and differentiated in CSF-1. We have performed surface marker analysis and gene expression profiling on macrophages from these compartments, comparing 25 animals from 5 different breeds and their response to lipopolysaccharide. The results provide a clear distinction between alveolar macrophages (AM) and monocyte-derived (MDM) and bone-marrow-derived macrophages (BMDM). In particular, the lung macrophages express the growth factor, Flt1 and its ligand, VEGFA at high levels, suggesting a distinct pathway of growth regulation. We confirm that pig macrophages more closely resemble human, than mouse, in their set of LPS-inducible genes. Relatively few genes showed breed-specific differential expression, notably CXCR2 and CD302 in alveolar macrophages. In contrast, there was substantial inter-individual variation between pigs within breeds, mostly affecting genes annotated as being involved in immune responses. Conclusions: Future research will address whether such variation is heritable, and might form the basis for selective breeding for disease resistance or functional genomics. The domestic pig (Sus scrofa) provides a large animal model for human innate immune responses and inflammation that is also economically important in its own right. We demonstrate that macrophages can be harvested from 3 different compartments of the pig (lungs, blood and bone-marrow), cryopreserved and subsequently recovered and differentiated in CSF-1. We have performed surface marker analysis and gene expression profiling on macrophages from these compartments, comparing 25 animals from 5 different breeds and their response to lipopolysaccharide. The results provide a clear distinction between alveolar macrophages (AM) and monocyte-derived (MDM) and bone-marrow-derived macrophages (BMDM). In particular, the lung macrophages express the growth factor, Flt1 and its ligand, VEGFA at high levels, suggesting a distinct pathway of growth regulation. We confirm that pig macrophages more closely resemble human, than mouse, in their set of LPS-inducible genes. Relatively few genes showed breed-specific differential expression, notably CXCR2 and CD302 in alveolar macrophages. In contrast, there was substantial inter-individual variation between pigs within breeds, mostly affecting genes annotated as being involved in immune responses. Future research will address whether such variation is heritable, and might form the basis for selective breeding for disease resistance or functional genomics. 140 Affymetrix Snowball microarray were analysed from 5 different breed (DR, LR, LW, PIE and HAM). 5 pig per breed were used and cells were harvested from Lungs, blood and bone-marrow (AM, MDM and BMDM). Cells were left untreated (0h) or stimulated with LPS Salmonella enterica serotype minnesota Re 595 - 100ng/ml (7h)

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Identification of molecular pathways in pigs with good and poor response to a porcine reproductive and respiratory syndrome (PRRS) genotype 1 vaccine strain.

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