Future concepts in combating uterine disease depend on understanding the mechanisms of infection and immunity

Dairy cows help feed the world by converting proteins from plants to higher value proteins in milk, which have a more appropriate essential amino acid profile for human consumption and are more readily digestible. Lactation depends on pregnancy but following uterine disease after parturition many dairy cows are infertile, which compromises global food security. Uterine disease is caused by Escherichia coli, Trueperella pyogenes, anaerobic bacteria and viruses. Specific strains of microbes are tropic for the uterus, including endometrial pathogenic E. coli (EnPEC) and Bovine Herpesvirus-4. In the endometrium, epithelial and stromal cells are the first line of defence against microbes and they have key roles in innate immunity. Endometrial cells possess Toll-like receptors to detect pathogen-associated molecular patterns, leading to the secretion of chemokines and cytokines, which attract macrophages and neutrophils. Uterine disease also compromises the function of ovarian follicles and the corpus luteum. Granulosa cells from ovarian follicles express Toll-like receptors, and pathogen-associated molecular patterns perturb their endocrine function, stimulate the secretion of inflammatory mediators and damage oocytes. The inflammatory response to microbes can be limited by treating endometrial cells with inhibitors that target intracellular signalling pathways. Understanding the mechanisms of infection and immunity in the female genital tract is driving smarter discovery of therapeutics to combat uterine disease.