Lactation stage impacts the glycolytic function of bovine CD4+ T cells during ex vivo activation

Authors: EDER, JORDAN - Iowa State University; GORDEN, PATRICK - Iowa State University; Lippolis, John; Reinhardt, Timothy; Sacco, Randy

Submitted to: Nature Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/10/2020
Publication Date: 3/4/2020
Citation: Eder, J.M., Gorden, P.J., Lippolis, J.D., Reinhardt, T.A., Sacco, R.E. 2020. Lactation stage impacts the glycolytic function of bovine CD4+ T cells during ex vivo activation. Nature Scientific Reports. 10(4045). https://doi.org/10.1038/s41598-020-60691-2.
DOI: https://doi.org/10.1038/s41598-020-60691-2

Interpretive Summary: With milk production and pregnancy in dairy cows come increased energy demands. Our interest in the present study was in examining the impact of the altered cow bodily processes during various stages of milk production on the function of a subset of white blood cells in dairy cows. The data shows that there are differences in the responsiveness of these white blood cells depending on stage of milk production, with the lowest responses in cells from cows in early stages of production. We would suggest that reduced function of these white blood cells in early stages of milk production may provide a partial explanation for the increased susceptibility of these cows to infections.

Technical Abstract: Dairy cattle undergo dynamic physiological changes over the course of a full lactation into the dry period. These physiological changes have been shown to impact the immunocompetence of dairy cows. During activation, T lymphocytes undergo a characteristic rewiring to increase the uptake of glucose and metabolically reprogram to support aerobic glycolysis concurrently with oxidative phosphorylation. To date it remains to be completely elucidated how the altered energetic demands associated with lactation in dairy cows impacts T cell metabolic reprogramming. Thus, we have examined the influence of stage of lactation on cellular metabolism in activated bovine CD4+ T cells Our ex vivo studies compared the effects of activation on metabolic function of CD4+ T cells from dairy cattle across a full lactation cycle, including the dry period. Results showed higher rates of glycolytic function and mitochondrial respiration in activated CD4+ T cells from late lactation and dry cows compared to cells from early and mid lactation cows. Similarly, protein and mRNA expression of cytokines were higher in CD4+ T cells during late lactation and dry cows than CD4+ T cells from mid and early lactation cows. On the other hand, gene expression of enzymes and signaling molecules involved in metabolic processes were comparable between CD4+ T cells from mid lactation cows and dry cows and were generally lower expressed than in cells from late lactation cows. Therefore, gene expression of molecules associated with metabolic processes are not likely an appropriate indicator of alterations in metabolic function. The data suggest CD4+ T cells from lactating cows have an altered metabolic responsiveness that could impact the immunocompetence of animals, particularly those in early lactation, and increase their susceptibility to infection.