Tuberculosis continues to be one of the greatest infectious disease threats to public health and treatments are becoming more limited. It is caused by human to human airborne transmission of Mycobacterium tuberculosis (M.tb), a bacterium adapted for life within the resident immune cell of the lung – the alveolar macrophage (AM). The inflammatory mechanisms of the AM are highly regulated to avoid damage to the delicate lung environment and as a result the killing ability of the AM is dampened when encountering the host-adapted M.tb. Understanding the detailed signaling pathways and biology that dictates AM development in the lung holds the key to new treatment and vaccine strategies. This new 5-year, $1,725,083 dollar NIH grant, titled “TB and Innate Immune Regulation of Lung Macrophages,” is to expand a fundamental discovery by the Schlesinger research team on a key regulator of lung macrophage biology, Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ), whose activity is enhanced by surfactant which the AMs are bathed in. Understanding how M.tb and different components of surfactant regulate PPAR-γ and its downstream immune-related functions will help decipher the molecular mechanisms underlying AM activation in response to M.tb and other intracellular pathogens. Thus, results from this research may identify PPAR-γ as a potential target for novel host-directed therapies for tuberculosis.