Nutrients and Immunometabolism: Role of Macrophages

Authors: Larson, Kate; ALVINE, TRAVIS - Former ARS Employee; Wu, Dayong; KALUPAHANA, NISHAN - University Of Peradeniya; MOUSTAID-MOUSS, NAIMA - Texas Tech University; Roemmich, James

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/6/2020
Publication Date: 4/9/2020
Citation: Larson, K.J., Alvine, T., Wu, D., Kalupahana, N., Moustaid-Mouss, N., Roemmich, J.N. 2020. Nutrients and immunometabolism: Role of macrophages. Journal of Nutrition. https://doi.org/10.1093/jn/nxaa085.
DOI: https://doi.org/10.1093/jn/nxaa085

Interpretive Summary: The immune system is complex being made-up of many unique and specialized immune cell types that vary in function. Although the primary function of the immune system is to monitor the internal environment of the body and provide defense against disease, immune cells are also involved in many non-defense related activities in almost every organ system. Aging, obesity, pregnancy, and chronic disease development uniquely alter the invader organisms and metabolites within the physiologic environment. In turn, immune cells alter the metabolic substrates and/or metabolic pathways that they use for energy and to mount an immune defense. In addition, immune cells interact with non-immune host cells to alter local and systemic inflammation. As chronic inflammation is a key determinant in the development of chronic disease and macrophages are the major contributors to the inflammation-associated metabolic diseases, this review focuses on the roles of macrophages in inflammation in pathological conditions. This review provided the most recent evidence regarding how macrophages, a critically important innate immune cell type, is activated by various stimuli to activate complex called NLRP3 inflammasome in key metabolic tissues. This review also summarized currently available evidence on how nutrients regulate NLRP3 inflammasome.

Technical Abstract: In a classical sense, inflammation is largely mediated by immune cells responding to invading pathogens while metabolism is oriented with producing usable energy for vital cell/tissue specific functions. As an increasing number of studies have addressed immunometabolic alterations, we now understand that regulation of inflammation affects metabolic pathways. This review provided the most recent evidence regarding how macrophages, a critically important innate immune cell type, is activated by various stimuli to activate complex called NLRP3 inflammasome in key metabolic tissues. This review also provides a current overview of how shifts in macrophage metabolism, changes in metabolic substrates, accumulation of metabolic intermediates, and endogenous molecules released from damaged organelles can exacerbate macrophage hypoxia and IL-1''production to activate NLRP3 inflammasome. This review summarized currently available evidence on how nutrients regulate NLRP3. NLRP3 inflammasome has been implicated in type 2 diabetes, Alzheimer's disease, liver diseases, and some infectious diseases, understanding nutrient- and cell type-specific regulation of inflammasome associated pathways is crucial for intervention strategies.