Abstract
Dairy cattle undergo dynamic physiological changes over the course of a full lactation into the dry period, which impacts their immunocompetence. During activation, T cells undergo a characteristic rewiring to increase the uptake of glucose and metabolically reprogram to favor aerobic glycolysis over 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, in our ex vivo studies we have examined the influence of stage of lactation (early lactation into the dry period) on cellular metabolism in activated bovine CD4+ T cells. Results showed higher rates of glycolytic function 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 from dry cows than CD4+ T cells from lactating cows. The data suggest CD4+ T cells from lactating cows have an altered metabolic responsiveness that could impact the immunocompetence of these animals, particularly those in early lactation, and increase their susceptibility to infection.
Highlights
Physiological stresses of pregnancy and lactation are energetically demanding, with glucose being shuttled to mammary glands and/or fetus depending on lactation stage and gestation[1]
Because energy balance is important in understanding physiology of lactation stage, we analyzed serum glucose, insulin, and non-esterified fatty acids (NEFAs) levels from cows in each stage
Our study provides novel data on the immunometabolic impact lactation has on activated CD4+ T cells
Summary
Physiological stresses of pregnancy and lactation are energetically demanding, with glucose being shuttled to mammary glands and/or fetus depending on lactation stage and gestation[1]. Metabolic reprogramming refers to “the Warburg effect”, a phenomenon first described in cancer cells, which utilize aerobic glycolysis in oxygen-rich environments[6]. This phenomenon has since been reported in many immune cells, including T cells[7,8,9,10]. CD4+ T cells in a resting state utilize oxidative phosphorylation, but with engagement of the T cell receptor (TCR) and CD28, glucose uptake is increased and downstream signaling within the cell occurs[4,11] This metabolic switch enables cells to utilize mitochondrial respiration, i.e. oxidative phosphorylation (OXPHOS) to upregulate mitochondrial biogenesis during activation to increase the generation of biomolecules necessary for clonal expansion[12,13] while simultaneously increasing the glycolytic rate of the cell. One-way ANOVA with Sidak’s multiple comparisons among all stages. *p < 0.05
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