Genomic variation in innate immunity and susceptibility to uterine diseases in Holstein cows

Abstract

Fertility is crucial for efficient dairy production, and adequate uterine health is a key element that allows for rapid resumption of reproductive function after calving. The challenge of uterine contamination with microorganisms at parturition is unavoidable. Some cows respond to this challenge successfully; however, approximately 20% of cows will develop metritis or clinical endometritis. Subsequently, the prevalence of subclinical endometritis will range from 25% to 75%. Innate immunity provides the first line of defense against infection by eliciting host responses to invading pathogens without requiring prior exposure. This response depends mainly on the action of neutrophils (PMNs) and macrophages with pattern recognition receptors that recognize molecular ligands from microbial species, which then initiate signaling pathways that result in the release of pro-inflammatory cytokines. One important group of receptors is the toll-like receptors (TLR), which regulate the activation of both innate and adaptive immunity. Likewise, the initial defense of the endometrium against invading microbes is dependent on the innate immune system, including initial recognition by host TLR proteins. Genetic selection for increased disease resistance in cattle has been proposed, and current molecular technologies provide the opportunity for exploring genomic variation related to health. We hypothesized that naturally occurring variation within the bovine TLR genes may be associated with differential susceptibility to reproductive diseases in Holstein cattle. The objective of this study was to test for associations between bovine single nucleotide polymorphisms (SNPs) and insertion-deletion (indel) mutations occurring in 7 bovine TLR genes (TLRsl, 2, 4, 5, 6, 9, and 10) that are known to recognize bacterial ligands and uterine diseases in dairy cows including metritis (MET), clinical endometritis (CE), and cytologic endometritis (CYE).