Neutrophil heterogeneity in health and disease: a revitalized avenue in inflammation and immunity

Leucocytes form the principal cellular components of immunity and inflammation, existing as multiple subsets defined by distinct phenotypic and functional profiles. To date, this has most notably been documented for lymphocytes and monocytes. In contrast, as neutrophils are traditionally considered, to be short-lived, terminally differentiated cells that do not re-circulate, the potential existence of distinct neutrophil subsets with functional and phenotypic heterogeneity has not been widely considered or explored. A growing body of evidence is now challenging this scenario, and there is significant evidence for the existence of different neutrophil subsets under both physiological and pathological conditions. This review will summarize the key findings that have triggered a renewed interest in neutrophil phenotypic changes, both in terms of functional implications and consequences within disease models. Special emphasis will be placed on the potential pro- and anti-inflammatory roles of neutrophil subsets, as indicated by the recent works in models of ischaemia-reperfusion injury, trauma, cancer and sepsis.