Genetic Mechanisms of Tissue-Resident Macrophage Maintenance and Function

Michigan State University College of Osteopathic Medicine's Applied Immunology Center for Education and Research (AICER), leads a research program focused on how tissue-resident macrophages in the lung maintain pulmonary function and mediate immune protection against Mycobacterium tuberculosis and other lung insults. Recognizing that tuberculosis remains a major global killer despite available antibiotics, this work aims to shorten lengthy treatment regimens and to identify host-directed therapeutic strategies that prevent progression to pulmonary TB disease. In July, Dr. Olive received two research awards totaling more than $4.6 million that will sustain and expand these efforts. A grant of approximately $2.6 million from the National Institute of Allergy and Infectious Disease (NIAID) will enable his team to employ tools they have developed to interrogate macrophage responses during infection with Mycobacterium tuberculosis, with the explicit goal of discovering interventions that reduce therapy time and improve clinical outcomes. A second award, in excess of $1.9 million from the National Institute of General Medical Sciences (NIGMS), supports work using a new model of lung-specific macrophages, alveolar macrophages, to probe fundamental aspects of lung biology.

The research bridges basic lung biology and translational immunology. By characterizing how alveolar macrophages are maintained under healthy conditions and how their functions change after exposure to pathogens or environmental pollutants, the project seeks to reveal mechanisms by which macrophages control inflammation and preserve lung function. Those mechanisms are central not only to host defense against TB but also to understanding lung damage caused by other infectious agents, including SARS-CoV-2, and by chronic conditions such as COPD, lung cancers, and autoimmune disorders like systemic lupus erythematosus. Through dissecting macrophage maintenance, function, and inflammatory control, Dr. Olive's lab aims to identify targets for therapies that limit inflammatory injury while enhancing protective immunity.

The combined awards provide resources to apply existing experimental toolsets to clinically relevant questions, to refine lung-specific macrophage models, and to pursue host-directed approaches that could shorten current TB treatment courses, which now require months of antibiotic therapy. By advancing understanding of tissue-resident macrophage biology in the lung, the research promises insights that could inform prevention and treatment strategies across a spectrum of pulmonary diseases, ultimately aiming to reduce disease burden and improve patient outcomes.