The complexity and challenge of studying tissue macrophages

Macrophages are myeloid immune cells that are strategically positioned throughout the body tissues, where they ingest and degrade dead cells, debris, and foreign material and orchestrate inflammatory processes. The recent past saw two major advances in our understanding of macrophage biology. First, most tissue-resident macrophage populations are now appreciated to be seeded through early embryonic waves of hematopoiesis and to self-maintain during adulthood independently of further hematopoietic input. Secondly, aside from being immune sentinels, tissue macrophages have emerged as integral components of their host tissue, that contribute to the development and specific function of their tissue of residence. Moreover, accumulating data point towards distinctive roles to subset macrophages according to their anatomical niche within the tissue (e.g. juxtaposition to blood vessels, neurons etc). Tissue and niche specialization is reflected in discrete gene signatures and enhancer landscapes of macrophages, that are established in response to local environmental cues.

To fully understand macrophage functions these cells have to be studies in their physiological niches. Moreover, the study of tissue macrophages poses unique challenges that require the development of new experimental approaches. Here we present recent efforts of the Jung laboratory to investigate macrophage functions in tissue context, with a particular focus on contributions to pathologies of the gut and the brain. Specifically, we adopted methods that allow to retrieve tissue macrophage translatomes without prior cell isolation and develop novel ‘split’ Cre recombinase-based methods to target macrophage subpopulations and probe their functions.