The innate immune system includes several different cell types, each with specialized roles. Hidalgo’s lab focuses primarily on two: neutrophils and macrophages.
Neutrophils, the most abundant immune cell, are produced in the bone marrow but move throughout the body, adapting to different environments. They have a lifespan of less than 24 hours, which means the body must continuously produce them, about 100 billion a day for a healthy adult.
For many years, scientists assumed neutrophils were uniform. But advances in imaging technology, as well as in flow cytometry and single-cell transcriptomics, have revealed something more complex. “It was a matter of resolution,” says Hidalgo. What once appeared to be a single cell type we now know to be multiple distinct states. “They’re coming in different flavors. They go to different places, and they do different things.”
More recently, Hidalgo, as part of an international consortium of scientists, generated a transcriptional map called NeuMap, the first comprehensive guide of neutrophil organization across tissues and disease states. Hidalgo’s lab continues to expand and refine this map to better understand how certain diseases impact the function of neutrophils, and to find ways to reprogram those cells to potentially benefit patients.
This insight into the heterogeneity of neutrophils has facilitated other discoveries from Hidalgo’s lab, including the role certain neutrophils play in building and maintaining healthy skin.
Macrophages are less abundant than neutrophils but are equally important in keeping our systems running optimally. They reside within tissues and interact closely with parenchymal cells, which are responsible for essential functions of our organs and include cardiomyocytes in the heart and hepatocytes in the liver. When macrophages are disrupted or depleted in an organ, it’s no longer able to sustain performance over time.
In a 2020 study published in Cell, Hidalgo and others found that cardiomyocytes, which allow the heart to pump in a coordinated, continuous manner, rely on macrophages to clear out mitochondria and other waste material. Depletion of those cardiac macrophages leads to the accumulation of discarded mitochondria, inflammation, organ dysfunction, and emergence of aging-like characteristics.