Alveolar Macrophages in Pulmonary Neuro-immune Communication

Abstract

Alveolar macrophages are strategically located at the lung mucosal surface and are part of an intricate cellular network. Here, immune cells, epithelial cells and neurons functionally interact to maintain homeostasis despite a multitude of aggressions and ever-changing environmental conditions. Previous evidence suggest that neuron-derived cues may modulate alveolar macrophages, but also indicate that immune cells influence neuronal activity. Thus, we hypothesized that alveolar macrophages functionally interact with neurons in so-called neuro-immune cell units. Nevertheless, the identity of these units and the nature of this communication remains unknown. Therefore, using advanced imaging techniques, molecular analyses and novel tracing techniques, we set out to define the bi-directional communication between alveolar macrophages and neurons. We found that alveolar macrophages and neurons co-localize. Using a novel tracing technique, we demonstrate that these cells may engage in bi-directional communication. We also show that alveolar macrophages possess the machinery to engage in neuro-immune crosstalk. These results can be easily expanded to fully assess this new neuro-immune cell unit. Furthermore, this versatile new tracing strategy can easily be applied to other neuro-immune cell units, allowing us to unravel this new paradigm in mammalian physiology. Ultimately, this will pave the way for the development of new therapeutic targets.