AUTHOR=Lange Shannon M., McKell Melanie C., Schmidt Stephanie M., Hossfeld Austin P., Chaturvedi Vandana, Kinder Jeremy M., McAlees Jaclyn W., Lewkowich Ian P., Way Sing Sing, Turner Joanne, Qualls Joseph E.
TITLE=l-Citrulline Metabolism in Mice Augments CD4+ T Cell Proliferation and Cytokine Production In Vitro, and Accumulation in the Mycobacteria-Infected Lung
JOURNAL=Frontiers in Immunology
VOLUME=8
YEAR=2017
URL=https://www.frontiersin.org/articles/10.3389/fimmu.2017.01561
DOI=10.3389/fimmu.2017.01561
ISSN=1664-3224
ABSTRACT=Activation, recruitment, and effector function of T lymphocytes are essential for control of mycobacterial infection. These processes are tightly regulated in T cells by the availability of l-arginine within the microenvironment. In turn, mycobacterial infection dampens T cell responsiveness through arginase induction in myeloid cells, promoting sequestration of l-arginine within the local milieu. Here, we show T cells can replenish intracellular l-arginine through metabolism of l-citrulline to mediate inflammatory function, allowing anti-mycobacterial T cells to overcome arginase-mediated suppression. Furthermore, T cell l-citrulline metabolism is necessary for accumulation of CD4+ T cells at the site of infection, suggesting this metabolic pathway is involved during anti-mycobacterial T cell immunity in vivo. Together, these findings establish a contribution for l-arginine synthesis by T cells during mycobacterial infection, and implicate l-citrulline as a potential immuno-nutrient to modulate host immunity.