Sex-specific metabolic programming in human neutrophil subsets.

Area of Science:

• Immunology
• Metabolism
• Cell Biology

Background:

• Sex differences in neutrophil metabolism are known, but their extension to specific neutrophil subsets is unclear.
• Low-density neutrophils (LDNs) are associated with disease and immune dysregulation.
• Normal-density neutrophils (NDNs) represent the majority of neutrophils in healthy individuals.

Purpose of the Study:

• To investigate sex differences in the metabolism of distinct neutrophil subsets (LDNs and NDNs).
• To determine if metabolic dimorphism observed in neutrophils extends to LDNs and NDNs.

Main Methods:

• Isolation of LDNs and NDNs from healthy human donors.
• Assessment of cellular metabolism, including oxidative phosphorylation and glycolysis.
• Flow cytometry analysis for maturity markers (CD16hi/lo).

Main Results:

• Male LDNs exhibited significantly higher basal oxygen consumption rate (OCR) and ATP production than female LDNs.
• No significant sex differences in metabolism were observed in NDNs.
• Male LDNs showed higher OCR and glycolysis compared to their matched NDNs, while female LDNs had lower OCR than their NDNs.
• Male LDNs display a hypermetabolic phenotype compared to female LDNs and NDNs.

Conclusions:

• Neutrophil LDNs exhibit subset-specific sexual metabolic reprogramming.
• Male LDNs possess a hypermetabolic phenotype.
• Findings provide a metabolic basis for sex-biased immune responses and underscore the need for sex-stratified approaches in neutrophil-targeted therapies.