Innate gene repression associated with Mycobacterium bovis infection in cattle: toward a gene signature of disease

<p>Abstract</p> <p>Background</p> <p>Bovine tuberculosis is an enduring disease of cattle that has significant repercussions for human health. The advent of high-throughput functional genomics technologies has facilitated large-scale analyses of the immune response to this disease that may ultimately lead to novel diagnostics and therapeutic targets. Analysis of mRNA abundance in peripheral blood mononuclear cells (PBMC) from six <it>Mycobacterium bovis </it>infected cattle and six non-infected controls was performed. A targeted immunospecific bovine cDNA microarray with duplicated spot features representing 1,391 genes was used to test the hypothesis that a distinct gene expression profile may exist in <it>M. bovis </it>infected animals <it>in vivo</it>.</p> <p>Results</p> <p>In total, 378 gene features were differentially expressed at the <it>P </it>≤ 0.05 level in bovine tuberculosis (BTB)-infected and control animals, of which 244 were expressed at lower levels (65%) in the infected group. Lower relative expression of key innate immune genes, including the Toll-like receptor 2 (<it>TLR2</it>) and <it>TLR4 </it>genes, lack of differential expression of indicator adaptive immune gene transcripts (<it>IFNG, IL2, IL4</it>), and lower <it>BOLA </it>major histocompatibility complex – class I (<it>BOLA</it>) and class II (<it>BOLA-DRA</it>) gene expression was consistent with innate immune gene repression in the BTB-infected animals. Supervised hierarchical cluster analysis and class prediction validation identified a panel of 15 genes predictive of disease status and selected gene transcripts were validated (<it>n </it>= 8 per group) by real time quantitative reverse transcription PCR.</p> <p>Conclusion</p> <p>These results suggest that large-scale expression profiling can identify gene signatures of disease in peripheral blood that can be used to classify animals on the basis of <it>in vivo </it>infection, in the absence of exogenous antigenic stimulation.</p

Innate gene repression associated with infection in cattle: toward a gene signature of disease-0

<p><b>Copyright information:</b></p><p>Taken from "Innate gene repression associated with infection in cattle: toward a gene signature of disease"</p><p>http://www.biomedcentral.com/1471-2164/8/400</p><p>BMC Genomics 2007;8():400-400.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2213678.</p><p></p>ected (A) and healthy control cattle (B). The lymphocyte and monocyte subpopulations are retained in peripheral blood mononuclear cells (PBMC)

Innate gene repression associated with infection in cattle: toward a gene signature of disease-4

<p><b>Copyright information:</b></p><p>Taken from "Innate gene repression associated with infection in cattle: toward a gene signature of disease"</p><p>http://www.biomedcentral.com/1471-2164/8/400</p><p>BMC Genomics 2007;8():400-400.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2213678.</p><p></p>ected (A) and healthy control cattle (B). The lymphocyte and monocyte subpopulations are retained in peripheral blood mononuclear cells (PBMC)

Innate gene repression associated with infection in cattle: toward a gene signature of disease-2

<p><b>Copyright information:</b></p><p>Taken from "Innate gene repression associated with infection in cattle: toward a gene signature of disease"</p><p>http://www.biomedcentral.com/1471-2164/8/400</p><p>BMC Genomics 2007;8():400-400.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2213678.</p><p></p>ing real time qRT-PCR. Fold change values are shown for PBMC from BTB-infected cattle (= 8) relative to PBMC from healthy control animals (= 8). Error bars show the standard error of the mean for each gene

Innate gene repression associated with infection in cattle: toward a gene signature of disease-1

<p><b>Copyright information:</b></p><p>Taken from "Innate gene repression associated with infection in cattle: toward a gene signature of disease"</p><p>http://www.biomedcentral.com/1471-2164/8/400</p><p>BMC Genomics 2007;8():400-400.</p><p>Published online 31 Oct 2007</p><p>PMCID:PMC2213678.</p><p></p> BTB-infected (= 6) and uninfected control animals (= 6) at two different alpha levels (≤ 0.05 and ≤ 0.01). For each value, the number of genes with increased or decreased expression is shown for the BTB-infected animals relative to the control animals (see Additional files and )