Highly interesting paper published by Nahrendorf et al (Immunity 2019) on tissue-specific macrophage responses to remote injury.
Taking an organism-wide perspective, we describe that macrophages react to infectious or distant ischemic stimuli. A priori, we expected variation in how different tissue-resident macrophages respond to disparate injuries. Gene expression profiles of macrophages in different tissue vary at baseline already, affecting cellular reaction to systemic cytokines. In addition, immune and stromal cell content varies across organs, which may influence the response of macrophages through reciprocal interaction of these cell types.
The gene expression atlas of macrophage response to injury (as illustrated in this interesting paper) strengthens the case for macrophages as therapeutic targets. Myeloid cells already hold interest in many disease and tissue settings; examples include tumor-associated macrophages and atherosclerotic plaques. The ongoing effort to shape macrophage activity with biologicals, RNAi, small-molecule inhibitors, and nanoparticle drug delivery may be broadened to consider macrophages organism-wide. Multiple organ failure commonly complicates the hospital course of patients with sepsis, stroke, or cardiogenic shock following acute myocardial infarction. Enhancing macrophages’ salutatory functions and dampening their deleterious inflammatory actions could mitigate complications and hasten recovery in such patients.
The full paper can be found here.