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The Nutrient-Sensing Kinase mTOR in Transition Cow Inflammatory Immune Dysfunction: A Novel Nutritional Intervention Target

Principal Investigator: Sabine Mann

Co-PI: Anja Sipka

Department of Population Medicine and Diagnostic Sciences
Sponsor: National Institute of Food And Agriculture-USDA
Grant Number: 2019-67015-29834
Title: The Nutrient-Sensing Kinase mTOR in Transition Cow Inflammatory Immune Dysfunction: A Novel Nutritional Intervention Target
Project Amount: $490,000
Project Period: July 2019 to June 2022

DESCRIPTION (provided by applicant):

Dairy cows suffer from infectious and inflammatory disease postpartum leading to significant economic loss, increased antimicrobial usage, and diminished animal welfare. The nutrient-sensing mechanistic target of rapamycin (mTOR) signaling pathway orchestrates immune cell proliferation and differentiation when amino acid (AA) and energy availability changes, regulates the inflammatory cytokine balance in innate immune cells, and provides a mechanistic link between metabolism and inflammation. Our global hypothesis is that activation of the mTOR pathway is reduced during the postpartum nutrient deficit. This alters the inflammatory response and causes immune dysregulation in transition cows. We hypothesize that increasing the AA availability in the immediate postpartum period increases the function of this nutrient-sensing pathway and improves the inflammatory cytokine balance postpartum. Objective 1: We determine the effect of pharmacological mTOR-pathway inhibition in bovine myeloid immune cells. Objective 2: We provide proof-of concept for our proposed nutritional intervention. We use intravenous supplementation of AA in the immediate postpartum period to stimulate mTOR activity in bovine immune cells and test the effect on the systemic inflammatory response to an intravenous LPS challenge. Objective 3: We test the ability of a transition cow AA diet supplementation strategy to alter the inflammatory response in dairy cows postpartum. Our work addresses the Animal Health and Disease (A1221) Program Area Priority as it focuses on maintaining healthy agriculture animals to ensure a safe and adequate food supply, by integrating cellular, mechanistic, and whole-animal aspects to study the innate immunity in transition dairy
cows.