Tpl2−/− macrophages exhibit impaired mitochondrial respiration and function in response to LPS stimulation.

Abstract Macrophages are instrumental in maintaining immune homeostasis, and their dysfunction or depletion is tied to many human diseases, including autoimmunity, obesity, cancer. Activated macrophages modify cellular metabolic pathways, such as glycolysis oxidative phosphorylation, drive diverse functions. Many processes occur the mitochondria, metabolite production, reactive oxygen species (ROS) generation. Previous research demonstrated that tumor progression locus 2 (Tpl2, MAP3K8, COT) required for induction of phosphorylation alternatively activated phenotype during Schistosome infection; however, Tpl2 regulation metabolism classically remains unexplored. We hypothesize normally promotes its absence causes mitochondrial dysfunction. LPS-stimulated Tpl2−/−bone marrow-derived (BMDMs) had decreased consumption, basal respiration, ATP maximal respiration compared wild type BMDMs. Additionally, Tpl2−/−BMDMs exhibited higher ROS production than These data suggest Tpl2−/−mitochondria functionally defective, TPL2 increases stress. Together, this may reveal underlying mechanism defective Tpl2−/−macrophage behavior. Understanding role will provide a foundation developing targeted therapies treat cancer autoimmune diseases. Supported by grant from NIH (R21 AI147003).