Associations between endometrial macrophages and persistence of endometritis in postpartum dairy cows

Cows can spontaneously recover from postpartum endometritis. An early predictive diagnosis could avoid unnecessary treatment of recovery cows thus limiting the emergence of antimicrobial resistance, and provide timed treatment to persistent cases. This study first characterised the presence, proportion and phenotype of endometrial macrophages (Mφ) in postpartum dairy cows (n = 173) with distinct endometrial health status. Neutrophils (PMN) and Mφ counts were evaluated in Diff-Quickstained uterine cytology slides at 21 and 42 days postpartum (DPP). At 21 DPP, the Mφ proportion was higher in cows later recovering than in cows with persistent endometritis until 42 DPP, and the PMN:Mφ ratio was higher in persistent than in recovery cows. Immuno-labelling showed that at 21 DPP, recovery cows had higher M2 (CD163+) counts and lower M1:M2 ratio than cows with persistent endometritis, whereas M1 (CD86+) counts were not different. Immuno-labelling of tissue sections from biopsy samples collected at 42 DPP showed that total Mφ and M2 counts were higher in cows with persistent endometritis than in recovery cows. In conclusion, results evidence that the persistence of endometritis is associated with a retarded/failure of Mφ-driven, namely M2-driven, pro-resolving mechanisms. This suggests that endometrial Mφ content at 21 DPP shows the potential to assist in predicting the recovery or persistence of postpartum endometritis in dairy cows, and prompts for comprehensive validation studies.