The role of neutrophil glycosylation in susceptibility to pneumonia after traumatic brain injury

The National Institute of Allergy and Infectious Diseases awarded Beth Israel Deaconess Medical Center, Inc. (doing business as BIDMC) $191,484 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to investigate the role of neutrophil glycosylation in pneumonia susceptibility following traumatic brain injury.

The research examines how damage-associated molecular patterns (DAMPs) released after trauma alter innate immune cell function and predispose patients to bacterial infection at barrier sites, particularly the lung. Post-traumatic pneumonia occurs in approximately 42% of traumatic brain injury patients and frequently necessitates tracheostomy, mechanical ventilation, and carries risk of death. Current preventive measures such as oral care and aspiration minimization do not fully resolve pneumonia risk because traumatic brain injury causes underlying immune dysregulation. The project focuses on glycomic alterations in leukocytes after trauma and how DAMPs, particularly heme released from intracellular compartments, regulate changes in the leukocyte glycome. Understanding these mechanisms offers opportunity for intervention to prevent post-traumatic infections.

The award carries a period of performance from September 1, 2026, through August 31, 2031, with place of performance in Boston, Massachusetts. This Project Grant is assistance funding under the Allergy and Infectious Diseases Research program, which supports biomedical research and research training in infectious diseases and related areas at public and private nonprofit institutions.

Abstract

Post-traumatic infections are a common cause of mortality in patients who suffer traumatic brain injury (TBI), with a documented incidence rate of approximately 42%. These pneumonias can be devastating, leading to need for tracheostomy, ongoing mechanical ventilation requirements, and death. While oral care and minimizing risk of aspiration can help avoid development of pneumonia, they do not completely resolve the issue, because TBI leads to underlying immune dysregulation that predisposes to pneumonia. Defining the mechanisms leading to this immune dysregulation provides an opportunity for intervention to prevent these devastating infections. Damage associated molecular patterns (damps) are circulating factors that are released from the tissue after trauma which can lead to profound susceptibility to bacterial infection at barrier sites like the lung. Heme, when released from the intracellular compartment, is particularly highly deleterious, exacerbating tissue damage and altering immune cell function. However, the mechanisms by which damps alter the function of the innate immune response are unclear, and this makes IT difficult to target an intervention to prevent these alterations. Glycomics has recently emerged as a critically understudied aspect of immunology, as glycans have a key role in the immune system and influencing cellular functionality. Glycans in glycoproteins and glycolipids are critical for signaling, cell-cell interactions, adhesion, and other functions of innate immune cells, and alterations in the glycome can have significant effects on leukocyte function. Alterations in the glycome of innate immune cells have never been studied after trauma. Moreover, the role of damps on this regulation is an entirely new area of study. This is a critical unmet need: by understanding how the leukocyte glycome changes after TBI and how that affects function, we can then design translatable therapies for humans to prevent post-TBI pneumonia. The long-term goal of this research is to leverage glycomic information that will inform potential personalized treatment of the TBI patient to avoid infection. Our central hypothesis is that there are identifiable damp- dependent glycomic signatures on innate immune cells after TBI that correlate to worsened bacterial clearance in the lung. Further, we posit that heme as a central damp, known to modulate glycosylation, is a central regulator. This approach would first identify changes in neutrophil glycosylation using our murine model and then correlate these changes in our repository of human blood samples to determine translatability. We will then study how scavenging and metabolizing heme after TBI using hemopexin may prevent these glycomic changes, thus providing a potential intervenable target to prevent TBI-induced immune dysregulation.