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Review
. 2017 Jun:46:1-7.
doi: 10.1016/j.coi.2017.03.008. Epub 2017 Mar 27.

Obesity altered T cell metabolism and the response to infection

William D Green  1 , Melinda A Beck  2
Affiliations
Review

Obesity altered T cell metabolism and the response to infection

William D Green et al. Curr Opin Immunol. 2017 Jun.

Abstract

An epidemic of obesity over the past three decades increases the risk of chronic and infectious diseases for adults and children alike. Within the past few years, obesity has been shown to impair the adaptive immune response to infection through alterations in T cell functioning. Growing evidence suggests that perturbations in T cell metabolism drives this stunted immune response, stemming from nutrient, hormone and adipokine dysregulation in the obese. In this review, recent findings in the fields of obesity and T cell mediated immunity demonstrate a unique relationship between altered mechanisms of T cell metabolic homeostasis and plasticity of adaptive immune responses in the obese setting.

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Conflict of interest statement

Conflicts of Interest: The authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
T cell metabolism and state of quiescent and activated T cells. Quiescent T cells utilize oxidative respiration of glucose-derived pyruvate as well as fatty acids and amino acids to produce ATP through the TCA cycle and electron transport chain. This energy production supports immune surveillance and homeostasis. Upon stimulation of the T cell receptor (TCR) and costimulatory receptors, T cells upregulate glycolysis and glutamine oxidation while reducing fatty acid oxidation to support cell growth, differentiation and the production of daughter cells. Following clearance of the pathogen, the majority of T cells undergo apoptosis with a subset surviving as memory T cells, which return to a quiescent state dependent on oxidative phosphorylation of fatty acids.
Figure 2
Figure 2
Mechanism of impairment of normal T cell signaling and response to infection in obesity. Nutrients, leptin and inflammation signals cause a disruption of normal T cell metabolism, resulting in impaired cellular functions. Long-term exposure to these extrinsic signals alters the metabolic profile of T cells, impacting their feedback of cytokine secretion and functional response to infection. Whether or not long-term exposure results in epigenetic changes, or metabolite influence from obese microbiota has yet to be determined.
See this image and copyright information in PMC

References

    1. van Panhuys N, Klauschen F, Germain RN. T-cell-receptor-dependent signal intensity dominantly controls CD4(+) T cell polarization In Vivo. Immunity. 2014;41:63–74. - PMC - PubMed
    1. Brownlie RJ, Zamoyska R. T cell receptor signalling networks: branched, diversified and bounded. Nat Rev Immunol. 2013;13:257–269. - PubMed
    1. Michalek RD, Gerriets VA, Jacobs SR, Macintyre AN, MacIver NJ, Mason EF, Sullivan SA, Nichols AG, Rathmell JC. Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets. J Immunol. 2011;186:3299–3303. - PMC - PubMed
    1. MacIver NJ, Michalek RD, Rathmell JC. Metabolic regulation of T lymphocytes. Annu Rev Immunol. 2013;31:259–283. - PMC - PubMed
    1. Buck MD, O’Sullivan D, Pearce EL. T cell metabolism drives immunity. J Exp Med. 2015;212:1345–1360. The authors provide a concise and expansive sumary of current knowledge on T cell metabolism and its contribution to the adaptive immune response. Topics discussed include metabolic states of T cells by different activation states and subsets as well as substrate utilization and function. - PMC - PubMed

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