The degree of postpartum metabolic challenge in dairy cows is associated with peripheral blood mononuclear cell transcriptome changes of the innate immune system

Dairy cows undergo a nutrient deficit immediately postpartum when lactational demands exceed nutrient intake. This occurs concurrently to an increased challenge due to bacterial and viral infections, yet ability for pathogen clearance is reduced despite a heightened and often host-damaging inflammatory response. We hypothesized that nutrient stress is associated with differences in the immune cell transcriptome. Our objective was therefore to investigate differentially expressed pathways (DEP) by RNA-seq in peripheral blood mononuclear cells harvested 3 weeks before and 1 week after calving from Holstein cows in low (L, n = 3) or high (H, n = 3) postpartum metabolic stress situations. Metabolic stress was defined by differences in circulating concentrations of glucose, fatty acids, and ketones postpartum. Cows in group H showed several upregulated DEP in relation to myeloid cell function and inflammatory response, as well as downregulation of the Th2 pathway. Principal components analysis showed that the transcriptome of group H postpartum samples was most different from all other samples. Differences in DE genes were noted even prepartum albeit fewer DE genes were identified and myeloid cell pathways in group H were generally downregulated at this time compared with group L. Samples within group L showed little difference between the two time points. We conclude that the metabolic phenotype of cows allowed us to identify differences in immune-regulatory pathways and that myeloid immune cells could play a dominant role in identifying these metabolically-associated differences that were demonstrated among a mixed mononuclear cell population.