When infection or injury occurs, neutrophils—our most abundant immune cells—are the first to arrive. Long considered short-lived foot soldiers of the immune system, they are essential for host defense yet notorious for exacerbating inflammation in conditions ranging from cardiovascular disease to COVID-19. Despite their ubiquity, scientists have struggled to understand how neutrophils function across tissues and disease states. Their substantial heterogeneity has been documented, but the lack of a unifying framework has limited translation into clinical insight.
That gap has now been addressed. An international consortium led by researchers at the Centro Nacional de Investigaciones Cardiovasculares (CNIC), Universidad Carlos III de Madrid (UC3M), Yale University, and Westlake University in China has created NeuMap, the first comprehensive atlas of neutrophils. The study published this week in Nature under the title “Architecture of the neutrophil compartment” analyzed more than one million cells using single-cell transcriptional profiling to chart how neutrophils are organized across tissues, developmental stages, and disease conditions in mice.
“What is most surprising,” explained Ivan Ballesteros, PhD, professor at UC3M and researcher at CNIC, “is that individual neutrophils live only a few hours, yet this cell population maintains a stable architecture throughout life. It is a pattern that emerges from chaos. Understanding this logic opens new avenues to guide immunity toward healing.”
NeuMap integrates data from 47 biological conditions, revealing that neutrophils organize into a finite number of functional hubs. These hubs represent distinct states: proliferative precursors, interferon-responsive cells, immunosuppressive subsets, and a silent circulating population. Computational modeling and timestamp analyses showed that neutrophils follow prototypical trajectories through these hubs, with preferred paths shifting depending on whether the body is in health, inflammation, or cancer, wrote the authors. “By integrating all these data,”—referring to a range of conditions from pregnancy and fetal development to infections, cancer, myocardial infarction, and aging—“we were able to observe how neutrophils follow common patterns despite their apparent diversity,” noted co-first author Daniela Cerezo Wallis, PhD, of Yale University.
The atlas also highlights molecular drivers of neutrophil fate. Signals such as TGFβ, IFNβ, and GM-CSF push the neutrophils along different trajectories, while chromatin accessibility mapping revealed that the transcription factor JUNB controls angiogenic and immunosuppressive states, promoting tissue revascularization.
Importantly, NeuMap’s architecture was shown to be conserved across sexes, environmental and genetic backgrounds, and even species, with human neutrophils displaying similar hubs. This conservation means the atlas may serve as a translational tool: by profiling blood neutrophils, researchers can infer the pathophysiological state of the host, added the authors. That opens the door to new biomarkers for infection, cancer, and cardiovascular disease, and potentially to therapies that redirect neutrophil trajectories.
“Our study delineates the global architecture of the neutrophil compartment and establishes a framework for exploration and exploitation of neutrophil biology, the researchers wrote. NeuMap provides a guide to navigate the immense heterogeneity of these cells, opening a new era in the understanding and control of the immune system.
