Systemic inflammation is typically observed in response to sepsis, but myocardial infarction (MI) and stroke can also have systemic immune effects, including the induction of emergency haematopoiesis. A new study shows that “macrophages everywhere in the body know when danger is afoot, even when the danger is distant,” explains Matthias Nahrendorf.

“We wondered if macrophages react to remote inflammation, how they might sense it and whether it matters to the host,” explains Nahrendorf. The researchers then challenged mice with MI, stroke or sepsis and examined subsequent changes in macrophage populations in the kidney, heart, liver and brain. “I was most surprised by the reduction in macrophages numbers, even in the kidney, shortly after the onset of bacteraemia,” notes Nahrendorf. “We looked at this carefully in the heart and found that macrophages take up circulating bacteria and then die.” After this initial sepsis-induced reduction, macrophages in the kidney cortex and medulla expanded and remained above normal levels for over 2 months, owing to both resident cell proliferation and recruitment of circulating cells. Injury, in particular sepsis, altered the gene expression profile of kidney macrophages, which was most similar to that of heart macrophages.

The researchers also noted that lung macrophages responded to MI with a strong upregulation of proliferation genes; this change was not seen after stroke or sepsis. “Unexpectedly, mice survived pneumonia better if they had a prior MI,” remarks Nahrendorf. “Lung macrophages seem to acquire a different phenotype after MI — we sometimes call it ‘bracing’ — that better prepares them for subsequent challenges,” explains Nahrendorf.

“We need to assess how long these changes in macrophage phenotypes persist, and we will follow up on differentially expressed genes,” adds Nahrendorf. “It would also be worthwhile to test whether chronic kidney disease induces changes in tissue macrophages throughout the body.”