Reproduction Abstracts (2014) 1 P293 | DOI: 10.1530/repabs.1.P293

Non-cytopathic BVDV suppressed innate immune response in bovine endometrial cells exposed to bacterial lipopolysaccharide

Chike Fidelis Oguejiofor, Zhangrui Cheng, Olivia Anstaett, Joe Brownlie, Ali A. Fouladi-Nashta & D Claire Wathes

Royal Veterinary College, Hatfield, Hertfordshire, UK.

Introduction: Infection with non-cytopathic BVDV (ncpBVDV) is associated with uterine disease and infertility in dairy cows although the underlying mechanisms are poorly understood. This project investigated the influence of ncpBVDV on innate immunity of the bovine endometrium.

Materials and methods: Primary bovine endometrial cells from each of six cows were divided into four groups (Control; LPS; BVDV; BVDV LPS). Cells were infected with ncpBVDV for 4 days followed by treatment with LPS for 6 h respectively. Whole-transcriptome gene expression was measured by Affymetrix Bovine Gene 1.1 Array containing the probes for 23000 transcripts.

Results and discussion: Analysis focusing on the comparison between BVDV LPS vs LPS groups showed 218 differentially expressed genes (P<0.05; ANOVA and paired t-test with BH adjustment). Of these, 192 genes were mapped and analysed with Ingenuity Pathway Analysis. The top two associated network functions were ‘Antimicrobial Response, Inflammatory Response, Infectious Disease’, score 33; and ‘Infectious Disease, Post-Translational Modification, Protein Folding’, score 31. The top Canonical Pathways were ‘Activation of IRF by Cytosolic Pattern Recognition Receptors’ and ‘Interferon Signalling’; P<0.001. Top down-regulated molecules (RSAD2, ISG15, BST2, MX2, USP18, IFIT3, IFI27, SAMD9, IFIT1, DDX58, IRF3 and MX1) are genes involved in innate immune signalling and the interferon pathway. Analysis of upstream regulators predicted the inhibition of IRF7, TLR3, IFNL1, IFNA2 and IFNB1.The results indicate that ncpBVDV suppressed a type 1 interferon/dsRNA recognition response in infected bovine endometrial cells exposed to bacterial LPS. The compromised immune state may predispose dairy cows to postpartum endometritis and a decrease in fertility.

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