Deciphering the mechanisms that regulate neutrophil recruitment and function in polytraumatic injury

The National Institute of Allergy and Infectious Diseases awarded Albert Einstein College of Medicine $100,228 on December 8, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to support research deciphering the mechanisms that regulate neutrophil recruitment and function in polytraumatic injury.

The research uses transgenic zebrafish larvae with fluorescently tagged neutrophils to visualize and track neutrophil behavior at the single-cell level in in-vivo polytraumatic injury models. The project examines how neutrophil recruitment differs between polytraumatic injuries—multiple concurrent injuries affecting distinct organs or systems—and single-injury models, with particular attention to dysfunction in neutrophil response when systemic inflammation is present. The work addresses the immune response mechanisms that determine outcomes following polytrauma, especially in patients with metabolic disorders such as diabetes and obesity who face elevated risk of secondary complications including nosocomial infections, impaired wound healing, and multi-organ dysfunction.

The assistance type is a Project Grant. Performance occurs in Bronx, New York, with a period of performance from the award date through March 31, 2028.

Abstract

Unintentional traumatic injuries are the leading cause of death in individuals under the age of 50, with a subset of patients suffering from polytraumatic injury. Polytrauma is characterized by multiple concurrent injuries, involving distinct organs or systems, with the potential for severe disability or death and despite medical advances to prevent immediate death due to exsanguination, mortality remains high. While the severity and location of these injuries are important, the immune response initiated after insult, which serves to limit further damage, is the key factor in determining outcome. Individuals with metabolic disorders, such as diabetes and obesity are at particularly high risk for secondary complications, due to their pre-existing systemic inflammation, making them susceptible to nosocomial infections, impaired wound healing, and multi-organ dysfunction (MODS). Neutrophils which are the first responders to sites of injury, are known for their rapid response to inflammatory signals. Our laboratory has previously shown that neutrophils are key mediators in this process and respond to early damage signals such as ATP and CA+2, which orchestrate the release of other chemoattractant gradients like CXCL8. Similarly, we have also shown that in the presence of systemic inflammation neutrophil response to single injuries is dysfunctional. While neutrophil response to single injury is well reported little is known about their response to polytraumatic injuries. Taking advantage of the zebrafish, we have developed multiple models to study polytraumatic injury in-vivo in a whole animal context. Using transgenic zebrafish larvae with fluorescently tagged neutrophils we can visualize and track neutrophils at the single cell level. Our data suggests that neutrophil recruitment to polytraumatic injuries is altered when compared to a single injury models. We observe neutrophils to prioritize complex organs, over simple organs such as the tailfin epithelium. Likewise, after inducing systemic inflammation, neutrophil recruitment to polytraumatic injuries is altered and prioritization to complex organs is no longer observed. Overall, this data suggests that neutrophil recruitment to polytraumatic injuries display different migration patterns, which are impacted by metainflammatory conditions. Therefore, we propose that unique and distinct chemotactic signals released by organs upon injury dictate neutrophil prioritization and modulate migration kinetics in polytraumatic injury. We aim to understand 1) the mechanisms that regulate neutrophil prioritization and heterogeneity to polytraumatic injury and to 2) explore the role of gpcr desensitization and recycling in neutrophil behavior in polytraumatic injury.