Global transcriptomic profiling of bovine endometrial immune response in vitro. II. Effect of bovine viral diarrhea virus on the endometrial response to lipopolysaccharide.
Infection with noncytopathic bovine viral diarrhea virus (ncpBVDV) is associated with uterine disease and infertility. This study investigated the influence of ncpBVDV on immune functions of the bovine endometrium by testing the response to bacterial lipopolysaccharide (LPS). Primary cultures of mixed epithelial and stromal cells were divided into four treatment groups (control [CONT], BVDV, CONT+LPS, and BVDV+LPS) and infected with ncpBVDV for 4 days followed by treatment with LPS for 6 h. Whole-transcriptomic gene expression was measured followed by Ingenuity Pathway Analysis. Differential expression of 184 genes was found between CONT and BVDV treatments, showing interplay between induction and inhibition of responses. Up-regulation of TLR3, complement, and chemotactic and TRIM factors by ncpBVDV all suggested an ongoing immune response to viral infection. Down-regulation of inflammatory cytokines, chemokines, CXCR4, and serine proteinase inhibitors suggested mechanisms by which ncpBVDV may simultaneously counter the host response. Comparison between BVDV+LPS and CONT+LPS treatments showed 218 differentially expressed genes. Canonical pathway analysis identified the key importance of interferon signaling. Top down-regulated genes were RSAD2, ISG15, BST2, MX2, OAS1, USP18, IFIT3, IFI27, SAMD9, IFIT1, and DDX58, whereas TRIM56, C3, and OLFML1 were most up-regulated. Many of these genes are also regulated by IFNT during maternal recognition of pregnancy. Many innate immune genes that typically respond to LPS were inhibited by ncpBVDV, including those involved in pathogen recognition, inflammation, interferon response, chemokines, tissue remodeling, cell migration, and cell death/survival. Infection with ncpBVDV can thus compromise immune function and pregnancy recognition, thereby potentially predisposing infected cows to postpartum bacterial endometritis and reduced fertility.
Department of Production and Population Health, Royal Veterinary College, North Mymms, Hertfordshire, United Kingdom.
Chike F
CF
Oguejiofor
Department of Production and Population Health, Royal Veterinary College, North Mymms, Hertfordshire, United Kingdom.
Zhangrui
Z
Cheng
Department of Production and Population Health, Royal Veterinary College, North Mymms, Hertfordshire, United Kingdom Life Science and Engineering College, Northwest University for Nationalities, Lanzhou, China.
Ayimuguli
A
Abudureyimu
Department of Pathology and Pathogen Biology, Royal Veterinary College, North Mymms, Hertfordshire, United Kingdom.
Olivia L
OL
Anstaett
Department of Pathology and Pathogen Biology, Royal Veterinary College, North Mymms, Hertfordshire, United Kingdom.
Joe
J
Brownlie
Department of Comparative Biomedical Sciences, Royal Veterinary College, North Mymms, Hertfordshire, United Kingdom.
Ali A
AA
Fouladi-Nashta
Department of Production and Population Health, Royal Veterinary College, North Mymms, Hertfordshire, United Kingdom dcwathes@rvc.ac.uk.
D Claire
DC
Wathes
D000818:Animals; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000276:immunology*; D002417:Cattle; D001908:Diarrhea Viruses, Bovine Viral; D004717:Endometrium / Q000187:drug effects / Q000276:immunology*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D011247:Pregnancy; D061251:Primary Cell Culture; D017154:Stromal Cells / Q000187:drug effects / Q000276:immunology; D014591:Uterine Diseases / Q000235:genetics / Q000276:immunology
D008070:Lipopolysaccharides
bovine viral diarrhea virus; endometrium; gene expression; innate immunity; uterine disease