Neutrophil Dynamics in Sepsis Pathophysiology

Neutrophils are the first responders in the innate immune defence against infection, yet in sepsis they can become both protectors and perpetrators of tissue injury. Under normal conditions, neutrophils undergo a tightly regulated sequence of rolling, adhesion, transmigration and microbial killing. In sepsis, however, chemokine receptor dysregulation and endothelial barrier alterations impair directed trafficking to infected tissues, while excessive neutrophil accumulation in non‐infected organs drives collateral damage. Metabolic reprogramming in sepsis, notably lactate accumulation, has been shown to delay neutrophil apoptosis through upregulation of immune checkpoint molecules, prolonging their pro‐inflammatory lifespan. Concurrently, release of neutrophil extracellular traps, proteolytic enzymes and reactive oxygen species contributes to endothelial disruption, coagulopathy and organ dysfunction. Advances in single‐cell profiling have unveiled diverse neutrophil subsets with distinct migratory, survival and immunomodulatory properties. This plasticity underpins the paradoxical role of neutrophils in sepsis pathophysiology, emphasising the need to balance effective microbial clearance with limiting host injury. A comprehensive understanding of the temporal and spatial regulation of neutrophil activation, death and heterogeneity is therefore essential to devise interventions that restore immune competence while mitigating organ failure.

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Neutrophil Dynamics in Sepsis Pathophysiology publication trend

The graph below shows the total number of articles in neutrophil dynamics in sepsis pathophysiology across all publications each year (not limited to Nature Index journals).

Technical terms

Chemotaxis: Directed migration of cells along chemical gradients.

Apoptosis: Programmed cell death characterised by membrane blebbing and DNA fragmentation.

PD-L1: Immune‐checkpoint ligand that inhibits apoptosis and modulates inflammatory signalling.

GPCR: G protein-coupled receptor, a membrane protein that transduces extracellular signals into cellular responses.

NETosis: A form of neutrophil cell death releasing chromatin-based traps to immobilise pathogens.

CXCR2/CXCR4: Chemokine receptors directing neutrophil egress from bone marrow and migration to tissues.

MCT1: Monocarboxylate transporter 1, facilitating cellular uptake of lactate.

ARDS: Acute respiratory distress syndrome, a severe lung inflammatory injury associated with hypoxaemia.

References

1. Enhanced lactate accumulation upregulates PD‐L1 expression to delay neutrophil apoptosis in sepsis. View (2023).
2. The role of G protein-coupled receptor in neutrophil dysfunction during sepsis-induced acute respiratory distress syndrome. Frontiers in Immunology (2023).
3. The Regulation of Neutrophil Migration in Patients with Sepsis: The Complexity of the Molecular Mechanisms and Their Modulation in Sepsis and the Heterogeneity of Sepsis Patients. Cells (2023).
4. Identification and characterization of neutrophil heterogeneity in sepsis. Critical Care (2021).