Distinct Transcriptional Responses across Tissue-Resident Macrophages to Short-Term and Long-Term Metabolic Challenge
Urszula Brykczynska, Marco Geigges, Sophia J. Wiedemann, Erez Dror, Marianne Böni‐Schnetzler, Christoph Hess, Marc Y. Donath, Renato Paro
Abstract
The innate immune system safeguards the organism from both pathogenic and environmental stressors. Also, physiologic levels of nutrients affect organismal and intra-cellular metabolism and challenge the immune system. In the long term, over-nutrition leads to low-grade systemic inflammation. Here, we investigate tissue-resident components of the innate immune system (macrophages) and their response to short- and long-term nutritional challenges. We analyze the transcriptomes of six tissue-resident macrophage populations upon acute feeding and identify adipose tissue macrophages and the IL-1 pathway as early sensors of metabolic changes. Furthermore, by comparing functional responses between macrophage subtypes, we propose a regulatory, anti-inflammatory role of heat shock proteins of the HSP70 family in response to long- and short-term metabolic challenges. Our data provide a resource for assessing the impact of nutrition and over-nutrition on the spectrum of macrophages across tissues with a potential for identification of systemic responses.