Immunometabolic networks during dendritic cell-Leishmania interactions

Abstract

The dynamic and complex metabolic coupling established between Leishmania and its host results from a long co-evolutionary process. Due to the constant and sudden alterations imposed by the host microenvironment, such metabolic coupling continues to be dynamically regulated. The constant pursuit and competition for nutrients within the host-Leishmania duet will alter the host metabolic pathways with significant consequences for its nutritional reserves, affecting the host cell phenotypic and functionality eventually. This is particularly relevant to immune cells, where perturbed host metabolic fluxes have crucial consequences of activating immune cells, eventuating their long-term functional changes and deciding the outcome of an infection. We and others have previously begun to identify perturbed metabolic niches and the involved actors on Leishmania-infected macrophages that are particularly relevant to the immune function. In addition to macrophages, Leishmania is also known to counteract and subvert host dendritic cells (DCs) responses, which are specialized antigen-presenting cells (APCs) that play a crucial role in driving adaptive immune responses. Perturbed metabolic fluxes on Leishmania-infected DCs are particularly relevant since it can crucially affect the activation, differentiation, and functions of this immune cell type and can deterministically direct the outcome of an infection. Here, we propose to generate the first comprehensive view on how L. infantum differentially modulate dendritic cell metabolic networks. Identifying these modified central metabolic nodes can be future targets for innovative prognostic, diagnostic, immunometabolic and therapeutic approaches. (AU)