What do immune cells “eat” when they are hungry?
Research in the Joseph Qualls Lab addresses how amino acid uptake and metabolism regulates immune cell function. L-arginine is a semi-essential amino acid required for microbicidal nitric oxide (NO) production by macrophages and for lymphocyte proliferation and effector functions. When L-arginine is limiting, these cells rely on its synthesis from a related amino acid, L-citrulline, to sustain their respective functions. Experimental mouse models, where the immune system is unable to convert L-citrulline to L-arginine, display increased susceptibility to avirulent and virulent mycobacterial infection in vivo.
Projects in our lab explore the metabolic consequences of L-arginine and L-citrulline in macrophages and T cells – two key immune cells required during host defenses against many bacterial pathogens, including Mycobacterium tuberculosis. Overall, our data show control of mycobacteria in vivo is dependent on L-arginine/L-citrulline metabolism, and targeting this pathway is a promising approach to enhance host defense during infection.