Abstract
The dysregulation of endometrial immune response to bacterial lipopolysaccharide (LPS) has been implicated in uterine disease and infertility in the postpartum dairy cow, although the mechanisms are not clear. Here, we investigated whole-transcriptomic gene expression in primary cultures of mixed bovine epithelial and stromal endometrial cells. Cultures were exposed to LPS for 6 h, and cellular response was measured by bovine microarray. Approximately 30% of the 1006 genes altered by LPS were classified as being involved in immune response. Cytokines and chemokines (IL1A, CX3CL1, CXCL2, and CCL5), interferon (IFN)-stimulated genes (RSAD2, MX2, OAS1, ISG15, and BST2), and the acute phase molecule SAA3 were the most up-regulated genes. Ingenuity Pathway Analysis identified up-regulation of many inflammatory cytokines and chemokines, which function to attract immune cells to the endometrium, together with vascular adhesion molecules and matrix metalloproteinases, which can facilitate immune cell migration from the tissue toward the uterine lumen. Increased expression of many IFN-signaling genes, immunoproteasomes, guanylate-binding proteins, and genes involved in the intracellular recognition of pathogens suggests important roles for these molecules in the innate defense against bacterial infections. Our findings confirmed the important role of endometrial cells in uterine innate immunity, whereas the global approach used identified several novel immune response pathways triggered by LPS in the endometrium. Additionally, many genes involved in endometrial response to the conceptus in early pregnancy were also altered by LPS, suggesting one mechanism whereby an ongoing response to infection may interfere with the establishment of pregnancy.
Highlights
Bacterial contamination of the uterus is observed in almost all dairy cows within the first two weeks after calving [1, 2]
30% of the 1,006 genes altered by LPS were classified as being involved in immune response
Increased expression of many IFN-signaling genes, immunoproteasomes, guanylate-binding proteins and genes involved in the intracellular recognition of pathogens suggests important roles of these molecules in 15 the innate defense against bacterial infections
Summary
Bacterial contamination of the uterus is observed in almost all dairy cows within the first two weeks after calving [1, 2]. Escherichia coli and Trueperella pyogenes were most prevalent in cows with uterine disease followed by anaerobic bacteria such as Fusobacterium, Prevotella and. The endometrium constitutes the first line of defense against such pathogens by mounting an innate immune response to eliminate the bacterial contaminants during uterine involution [6]. To specialized immune cells, endometrial epithelial and stromal cells possess pattern recognition receptors (PRRs) including toll-like receptors (TLRs) which detect pathogen-associated molecules such as bacterial lipopolysaccharide (LPS) [8]. Become compromised after calving, resulting in the development of inflammatory disease: clinical and subclinical endometritis are present in up to
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