Linking receptor-mediated phagocytosis and cAMP pathways in macrophage responses to tuberculosis

In 2017, an estimated 10 million people developed TB disease, demonstrating an urgent need for new approaches to therapy, including host-directed therapy (HDT), to halt infection and progression of active TB. To this end, the overall goal of our ongoing research program is to identify intracellular ?master regulators? of inflammation and metabolic intermediates that dictate human macrophage responses to Mycobacterium tuberculosis infection as a strategy to identify potential host cell targets for HDT. We hypothesize that mannose receptor ligation by M.tb initiates the cAMP signaling pathway leading to PPAR? activation, resulting in enhanced survival of M.tb in macrophages. The studies herein represent key steps in elucidating the mechanisms of cAMP regulation of PPAR?, critical players at the interface of host-pathogen interaction, in human macrophages.