Whole blood response to lipopolysaccharide depends on both physiological and genetic factors in dairy cattle

Immunity plays a pivotal role in productivity, health, and overall welfare in dairy cattle. This study aimed to investigate the genetic and physiological factors influencing the capacity of dairy cows to mount an immune response, with a focus on cytokine secretion and their relationship with lactation rank, milk production, udder health and ketosis-related traits. An approach combining ex vivo stimulation of whole blood using lipopolysaccharide (LPS) and Luminex^® technology-based cytokine assay was employed to assess response profiles in dairy cows from a divergent selection for mastitis resistance. Cytokine concentrations increased in relation to the lactation rank in the absence of stimulation. Cows with higher breeding values for somatic cell count exhibited lower CCL3 chemokine secretion and cytokines related to type 2 (IL-4) and type 3 (IL-17A) cell-mediated responses, suggesting a biased adaptive response against udder infections. Upon LPS stimulation, higher concentrations of β-hydroxybutyrate (BHB), indicative of ketosis, were associated with altered cytokine secretion patterns, especially with increased pro-inflammatory cytokines. In addition, cows with high milk production exhibited reduced basal secretion of inflammatory cytokines and displayed a capacity for a more balanced adaptive immune response under the LPS condition. Clustering analyses confirmed the cumulative effect of lactation rank and occurrence of ketosis on the response patterns. This study provides novel insights into how factors influence the immune response in dairy cows, offering potential implications for targeted interventions and breeding strategies to enhance disease resistance and overall animal health in dairy farming practices.