Abstract

A fundamental advance in the last decade or so has been the realization that resident macrophages are key elements of everyday tissue function, rather than mere immune sentinels. Studies have established, for example, roles for macrophages as diverse as iron recycling in the spleen or synaptic maintenance in the brain. Exploration of how macrophages participate in tissue physiology is therefore reshaping our perception of how tissues function in homeostasis, and how they respond to stress. In the particular case of the heart, the contribution of macrophages to normal organ homeostasis remains largely enigmatic.

Only recent studies have discovered that macrophages located in a small region of the heart (the atrioventricular node) are important for normal electrical conductance by regulating the membrane potential of cardiomyocytes (Hulsmans, Cell 2017). Beyond electrical conduction, however, a defining feature of cardiomyocytes is their massive demand for energy which is needed to keep hearts beating during our entire lives, and relies on a large pool of mitochondria to produce vast amounts of ATP. Because cardiomyocytes are long-lived and rarely (if ever) renew, a conceptually major challenge for these cells is to keep this pool of mitochondria functional at all times.

The classical view is that cardiomyocytes resort to intracellular mitophagy to eliminate dysfunctional organelles that can then be replaced by new ones; however, this model is challenged by the massive number of mitochondria in an adult cardiomyocyte (about 40% of its volume!), and a fully packed cytoplasm that makes autophagosome formation and transport to lysosomes difficult. In this seminar I will discuss basic features of tissue-resident macrophages and then focus on the particular functions that we have discovered in the heart of adult mammals, including their capacity to support mitochondrial fitness in cardiomyocytes. The ultimate goal is to illustrate the ever-expanding roles of innate immune cells in physiology, and to highlight the concept of immune-parenchymal crosstalk in everyday tissue function.