Characterisation of peripheral blood mononuclear cell populations in periparturient dairy cows that develop metritis

Abstract

Bacterial contamination of the uterus following calving is ubiquitous in the dairy cow, 40% of cows develop postpartum uterine infection, including metritis. While predisposing factors like twinning and dystocia are associated with metritis, it is unclear why some cows remain healthy following calving and others develop uterine infection, negatively impacting animal health, milk production and economic return. Here, we profiled peripheral blood mononuclear cells of cows before calving and during postpartum metritis. We hypothesized that peripheral blood mononuclear cell function and proportions would be altered during the prepartum period in cows that develop postpartum metritis. Using flow cytometry we observed reduced proportions of peripheral CD3/CD4, CD4/CD62L, FOXP3 and CD21 populations from -10 to 40 days relative to calving associated with metritis, while the proportion of peripheral CD3/CD4 lymphocytes were specifically reduced in the prepartum period before the onset of metritis. Peripheral blood mononuclear cells from cows with metritis had a perturbed capacity to secrete IL-1β or IFNγ in response to in vitro stimulus; cells collected during the prepartum period from cows that would go on to develop metritis failed to increase IL-1β secretion in response to stimulation, while IFNγ secretion was altered at calving and postpartum in cows with metritis compared to healthy herd mates. No effect of metritis was observed in the capacity of cows to mount a humoral immune response to antigen administered on the day of calving. The studies discussed here suggest that while minor changes to the prepartum immune system are observed in cows that develop metritis, changes observed in the postpartum period are more prevalent and likely a consequences of disease and not causative. Future studies to modulate the prepartum immune system may help to limit postpartum metritis.

Indicators of immunosuppression peripartum in dual purpose cows in the tropics affected health, productive and reproductive parameters

“…The leukocyte and neutrophil population diminished more in cows suffering clinical endometritis compared to healthy bovine animals. Results of this study were consistent with the reported data on specialized dairy cattle (Islam et al, 2014;Bromfield et al, 2018) from which not only a decline in the population of neutrophils has been informed but also in their immunological capacity and still, a greater loss of such in the cows having metritis (McDougall et al, 2017;Kimura et al, 2014).…”

“…The cows suffering clinical endometritis had a lower production of milk compared to the healthy cows, which conformed with the majority of the studies consulted (Bromfield et al, 2018;Giuliodori et al, 2013;Wittrock et al, 2011;Dubuc et al, 2011). These similarities can be explained by the fact that all cows with infectious processes reduce the consumption of the dry matter, which decreases the level of available energy for milk synthesis, in comparison with the healthy cows.…”

Neutrophil β-defensin gene expression of postpartum dairy cows is altered by prepartum dietary cation-anion difference

“…This coincides with reports that treatment of hypocalcemia with an oral Ca bolus, which results in a transient recovery of serum Ca, did not improve neutrophil functions (Miltenburg et al, 2018), whereas a sustained increase of Ca from calcitriol treatment or prevention of hypocalcemia from feeding a prepartum negative DCAD improved neutrophil function (Vieira-Neto et al, 2017). Postpartum immune dysfunction is associated with increased risk of postpartum diseases, such as metritis (Galvão et al, 2012;Bromfield et al, 2018). We observed that DEFB7, DEFB10, and LAP transcripts in LPS-stimulated neutrophils were decreased in cows that experienced metritis compared with cows that did not.…”

A Fixed Cohort Field Study of Gene Expression in Circulating Leukocytes From Dairy Cows With and Without Mastitis

“…Given the variability in homeorhetic responses to diverse diseases, identifying common, conserved resistance and tolerance mechanisms should provide insight into resilience in the face of pathogenic microbes from different sites of infection. For example, altered expression profiles of peripheral leukocyte immune regulatory genes related to trafficking, migration, adhesion, energy metabolism, inflammatory mediators, cytokines, cell survival and apoptosis have been associated with both mastitis and uterine disease (13)(14)(15)(16)(17). These findings suggest that changes in peripheral leukocyte gene expression may emphasize mechanisms of immunity that bridge disease states and target tissues.…”