Innate immunity mechanisms of the equine endometrium-benefit or harm?

Abstract

The reason for the increased susceptibility of some mares towards persistent post-breeding endometritis ("susceptible mares") is still undetermined. The equine endometrium is equipped with innate immunity mechanisms and the immunomodulatory enzyme indole-amine 2,3-dioxygenase (IDO). Endometrial epithelial cells represent the main resident cell population with afferent and efferent innate immune functions. They express Toll-like receptors (TLRs) 2, 4 and 6, the antimicrobial peptide beta-defensin and IDO. TLRs and beta-defensins are involved in bacterial defences, whereas IDO restricts bacterial growth and prevents exaggerated immune responses. The orderly expression of these components is beneficial for uterine health. Their dysregulation can evoke cellular injury, reduced bacterial defence and ongoing inflammation. Thus, it appears likely that a dysfunctional expression of one or several of these factors can predispose mares to persistent endometritis. Glands with endometrosis have an aberrant beta-defensin and IDO expression, i.e. in comparison to healthy glands immunostaining for beta-defensin is increased and IDO immunolabelling is diminished. Regarding their endometrial IDO expression, mares can be divided into 2 groups. The majority shows a strong IDO immunoreactivity in glandular epithelia (defined as group 1 mares), whereas glandular epithelia of some mares are mostly immunonegative (defined as group 2 mares). These data suggest that the clinical manifestation "susceptible mare" may be caused by different types of immunological dysfunctions including an overstimulation of TLRs, aberrant immune mechanisms associated with higher degrees of endometrosis or a reduced glandular IDO production. For future comparative studies on susceptible and resistant mares, the endometrial biopsy is a necessary tool, since it allows the direct correlation between histopathological findings and the expression of immunological components.