Reduced Oxidative Burst by Primed Neutrophils in the Elderly Individuals Is Associated With Increased Levels of the CD16^bright/CD62L^dimImmunosuppressive Subset

Abstract

The aim of our study was to analyze polymorphonuclear neutrophil (PMN) functions in elderly individuals compared with those in healthy young participants, directly in whole blood to avoid issues with data interpretation related to cell isolation procedures. Despite the presence of increased circulating levels of proinflammatory cytokines, resting PMNs from the elderly individuals were not activated as shown by normal CD62L and CD11b expression at the PMN surface and normal constitutive reactive oxygen species (ROS) production. However, suboptimal stimulation induced modulations of CD62L and CD11b expression, which positively correlated with the interleukin-6 circulating level, suggesting a possible in vivo preactivation of old PMNs by this cytokine. In addition, PMN phagocytosis of opsonized Escherichia Coli was decreased in elderly individuals. Furthermore, upon preincubation of elderly whole-blood samples with tumor necrosis factor-α or Toll Receptor agonists, we observed a reduced PMN oxidative burst in response to formyl peptides. Elderly participants also exhibited an increased percentage of the immunosuppressive CD16/CD62L PMN subpopulation, which was characterized by a lower phagocytic index and a reduced ROS production compared with the CD16/CD62L subset. Thus, the reduced phagocytosis and ROS production associated with an expansion of immunosuppressive CD16/CD62L PMN subpopulation might be involved in the increased susceptibility to bacterial and fungal infections with old age.

Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study

“…The increase in mature neutrophil numbers is most likely a result of glucocorticoid-induced demargination [39], as up to 50% of neutrophils are marginated in the endovascular lining in the noninjured state and can be very rapidly mobilised into the circulation to produce the neutrophilia of trauma. Compared to their CD16 BRIGHT CD62L BRIGHT counterparts, CD16 BRIGHT CD62L DIM neutrophils exhibit reduced ROS production, a trait shared by IGs, who also show reduced responsiveness to fMLF challenge [40–42]. Thus, the heterogeneous neutrophil pool consisting of highly mature subsets and IGs that developed postinjury could be 1 factor underlying the altered neutrophil function we describe here.…”

Neutrophil hyperactivation correlates with Alzheimer's disease progression

“…22 To investigate the senescent C-X-C chemokine receptor type 4 (CXCR4) high /CD62L low neutrophil subset, samples kept on ice were incubated for 45 minutes with phycoerythrin (PE)/cyanine 7 (Cy7)/antihuman CXCR4 (clone 12G5; Sony Biotech, San Jose, CA), PE/antihuman CD11b (clone ICRF44; BD Biosciences, San Jose, CA), and allophycocyanin (APC)/antihuman CD62L (BD Biosciences). 22 To investigate the senescent C-X-C chemokine receptor type 4 (CXCR4) high /CD62L low neutrophil subset, samples kept on ice were incubated for 45 minutes with phycoerythrin (PE)/cyanine 7 (Cy7)/antihuman CXCR4 (clone 12G5; Sony Biotech, San Jose, CA), PE/antihuman CD11b (clone ICRF44; BD Biosciences, San Jose, CA), and allophycocyanin (APC)/antihuman CD62L (BD Biosciences).…”

“…Differential phenotypic and functional features of neutrophils from AD-MCI and AD-D patients might be related to an imbalance between neutrophils subsets, that is, the overly active subset of senescent CXCR4 high neutrophils 40 and the immunosuppressive CD16 bright /CD62L dim subset of neutrophils exhibiting decreased proinflammatory properties 22,41,42 We observed an expansion of the senescent CXCR4 high /CD62L low subset of neutrophils in both groups of patients, and the percentage of neutrophils in the senescent subset was higher in AD-D than in AD-MCI patients (Fig 2A,C). Differential phenotypic and functional features of neutrophils from AD-MCI and AD-D patients might be related to an imbalance between neutrophils subsets, that is, the overly active subset of senescent CXCR4 high neutrophils 40 and the immunosuppressive CD16 bright /CD62L dim subset of neutrophils exhibiting decreased proinflammatory properties 22,41,42 We observed an expansion of the senescent CXCR4 high /CD62L low subset of neutrophils in both groups of patients, and the percentage of neutrophils in the senescent subset was higher in AD-D than in AD-MCI patients (Fig 2A,C).…”

Subsetting reveals CD16high CD62Ldim neutrophils in chronic rhinosinusitis with nasal polyps

“…In contrast, CD16 high CD62L dim neutrophils from elderly patients had a lower phagocytic index and exhibited a lower oxidative burst compared with the mature neutrophil subset. 6 However, these subsets were Since Pillay et al identified CD16 high CD62L dim neutrophils, this subset has mostly been studied in cancer. CD16 high CD62L dim neutrophils were prone to migrate into the tumor in patients with head and neck squamous cell carcinoma (HNSCC), due to increased CD11b and CD18 expression, and inhibited migration and proliferation and induced apoptosis of FaDu cancer cells.…”