Impact of high salt diet on CD8 T cell responses to acute viral infection

About This Grant

PROJECT SUMMARY/ABSTRACT Chronic diseases affect ~60% of the US population and many of these diseases have been linked to changes to the modern diet. Among these changes has been an increase in the consumption of ultraprocessed food containing very high salt contents. Salt is critical to human health since it provides a source of sodium required to maintain tissue homeostasis and support various physiological functions. However, excess salt consumption can be detrimental to human health. In addition to causing hypertension, excessive salt consumption can have an impact on immune function. Recent studies have demonstrated an impact of high salt diets on certain innate immune functions, on CD4 T cell differentiation and function and may temporarily enhance the CD8 T cell response to certain tumors. However, little is known about the impact of excessive salt consumption on CD8 T cell responses to viral infections. Our new preliminary data demonstrate that mice fed a high salt diet have reduced CD8 T cell function during an acute viral infection leading to a delay in viral clearance and an increase in virus-induced morbidity. In addition, virus-specific CD8 T cells from mice fed a high salt diet adopt a functional and phenotypic profile reminiscent of T cell exhaustion that normally occurs only during chronic viral infection. Thus, our data support that excessive salt consumption impairs CD8 T cell responses to viral infection and favors the development of T cell exhaustion. In this proposal, we will test the central hypothesis that excessive salt consumption rapidly impairs the capacity of CD8 T cells to respond to viral infections through both extrinsic and intrinsic mechanisms. We will address this hypothesis with 2 specific aims. In specific aim 1, we will determine the extrinsic T cell mechanisms through which excessive salt consumption impairs CD8 T cell responses to viral infection. In specific aim 2, we will identify the intrinsic T cell mechanisms by which excessive salt consumption impairs CD8 T cell responses to acute viral infections. Our work will reveal the fundamental biology underlying the regulation of CD8 T cell function by a key nutrient that is overconsumed by a large proportion of the human population. In addition, our research will provide new therapeutic targets and/or dietary interventions aimed at restoring CD8 T cell function in patients who consume excess dietary salt and experience viral infections. Thus, this work has the potential to significantly improve human health outcomes.