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Peripheral blood polymorphonuclear leukocytes (PMNs), the most abundant circulating white blood cells, account for 45–75% of circulating leukocytes. An estimated 10¹¹ PMNs are released from the bone marrow daily to maintain a continuous supply of these crucial yet short-lived terminally differentiated cells. PMNs circulate throughout the body and therefore can potentially impact every tissue. They are rapid early responders to sites of infection or tissue injury and have high phagocytic and inflammatory capacity to limit pathogen spread. PMNs also contribute to chronic sterile inflammatory diseases such as gout in which they periodically accumulate and reactivate in afflicted joints causing debilitating pain in patients [7].

Despite their abundance and high inflammatory capacity, PMNs are less well characterized in the field of aging immunology. PMNs from older donors have lower TLR1 expression that correlates with reduced activation of TLR1-dependent IL-8, CD11b, and glucose uptake [8]. While PMNs from healthy elderly donors have reduced phagocytic (FITC-labeled E. coli) capacity and increased superoxide in response to fMLP and PMA [9, 10], generalization of these findings has been complicated by differences noted from different stimuli and experimental conditions [11]. PMNs from elderly individuals also show reduced actin polymerization [12, 13], suggesting impairments in chemotaxis. Indeed, in support of this possibility, PMNs isolated from aged mouse bone marrow exhibited reduced chemotaxis [14]. In the aged, poor chemotaxis is proposed to prolong PMN presence in tissue, causing collateral tissue damage [14, 15].

PMNs can undergo a novel form of cell death, NETosis, in which DNA content containing digestive and inflammatory enzymes is extruded from the cell. NETosis is a unique method to control pathogenic spread but is also recently implicated in sterile inflammation [16–18]. PMNs from old mice have impaired ability to undergo NETosis in response to in vivo cecal ligation and puncture-induced model of sepsis and also in vitro after stimulation with TLR2 ligands, suggesting a cell-intrinsic defect in signaling to induce NET formation and/or extrusion [19, 20]. In parallel with these impairments, however, human PMNs from healthy older donors maintain their ability to activate the NLRP3 inflammasome when stimulated in vitro [21]. Despite certain PMN functions being retained during aging, the accumulated defects that have been identified outnumber them, and these multiple defects in critical early responding cells allow more rapid pathogenic spread early after infection, putting the elderly host at increased susceptibility to infection and morbidity.