LAUSR

Macrophages are dynamic and heterogenous group of immune cells that play multiple instrumental roles in homeostasis, surveillance and host defence. Owing to their remarkable functional plasticity, macrophages are involved in the initiation, amplification, and termination of immune responses. The localization of macrophages in a variety of tissues and their capacity to respond in a timely manner to a plethora of stimuli such as pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) underscores their importance in the modulation of inflammatory responses. Distinct pathogens induce characteristic and divergent profiles of macrophage activation that can either boost or dampen inflammation. Besides PAMPs, DAMPs released by injured or stressed cells during sterile inflammatory processes contribute to the shaping of macrophage phenotype. Macrophages are major determinants in disease models that are linked to sterile inflammation. Pathogenesis of sterile inflammatory diseases including metabolic diseases is affected by macrophage activity. In all these instances, macrophages orchestrate immune responses through close interactions with both immune and non-immune cells. Our aim with this Frontiers in Immunology Research Topic “Macrophage Plasticity in Sterile and Pathogen-Induced Inflammation” is to showcase some of the latest mechanistic insights into how macrophages control responses to pathogens and sterile inflammatory insults. We herein give an overview of this Frontiers in Immunology topic which includes 9 original articles and 8 (mini) review articles. Pantazi et al. describe a novel mechanism by which activation of angiotensin converting enzyme 2 (ACE2) may form the basis of an anti-inflammatory therapy that blocks the cytokine storm observed in COVID-19 patients. They propose that treatment of macrophages with the SARS-CoV-2 spike (S) protein results in the hyper-responsiveness of macrophages to Toll-like receptor (TLR) signals thereby promoting expression of pro-inflammatory mediators. The authors present evidence that treatment with S protein suppresses the inactive kinase isoform of IL-1R-associated kinase (IRAK)-M that is a central regulator of TLR responsiveness. They conclude that activation of ACE2 may represent a therapeutic strategy to interfere with the development of cytokine storm observed in COVID-19 patients.