Not So Sweet: Characterizing Neutrophil Swarming Dysfunction in Patients with Diabetes Mellitus
Abstract
Diabetes mellitus (DM), a chronic illness resulting in hyperglycemia and chronic inflammation, affects millions of people worldwide [1]. Hyperglycemia and chronic inflammation are known to cause immune cell dysregulation, leading to immunocompromise. As a result, DM patients have increased incidence of fungal infection, including those caused by Candida species, like Candida albicans [2]. Neutrophils, a primary innate cell, are first responders to fungal infection and deploy a wide range of weapons to eliminate pathogens. In DM, neutrophil functions become dysregulated [3, 4]. Many of these functions have been studied in DM; however, a novel function, termed neutrophil swarming, has only recently begun to be characterized. In swarming, neutrophils organize a collective response against a target that may not otherwise be able to be eliminated by individual neutrophils alone. Neutrophil swarming functions in DM have yet to be investigated. We hypothesized that patients with uncontrolled diabetes (defined here as A1C > 10%)) would have defective neutrophil swarming and fungal clearance. To address this knowledge gap, we leveraged a microscale printing assay to target fungal hyphae and elucidate the impacts of diabetes on neutrophil swarming. To do this, 8x8 grids of Poly-l-lysine were printed onto glass slides using a Picospotter (PolyPico, Galway, Ireland) and C. albicans hyphae were attached to each spot. Timelapse microscopy was used to observe neutrophil swarming events in response to these fungal targets. Isolated human neutrophils from healthy individuals were compared to neutrophils from patients with uncontrolled diabetes. We show that most individuals with diabetes have reduced capacity for neutrophil swarming as well as a significant reduction in fungal killing abilities in comparison to healthy controls. Lastly, we show that defective swarm responses of diabetic neutrophils can be rescued with G-CSF (growth-colony stimulating factor) treatment revealing potential therapeutic avenues for patients with diabetes or those who are immunocompromised.
Start Time
15-4-2026 1:30 PM
End Time
15-4-2026 4:30 PM
Room Number
Culp Ballroom 316
Poster Number
27
Presentation Type
Poster
Presentation Subtype
Posters - Competitive
Presentation Category
Science, Technology, and Engineering
Student Type
Graduate and Professional Degree Students, Residents, Fellows
Faculty Mentor
Alex Hopke
Not So Sweet: Characterizing Neutrophil Swarming Dysfunction in Patients with Diabetes Mellitus
Culp Ballroom 316
Diabetes mellitus (DM), a chronic illness resulting in hyperglycemia and chronic inflammation, affects millions of people worldwide [1]. Hyperglycemia and chronic inflammation are known to cause immune cell dysregulation, leading to immunocompromise. As a result, DM patients have increased incidence of fungal infection, including those caused by Candida species, like Candida albicans [2]. Neutrophils, a primary innate cell, are first responders to fungal infection and deploy a wide range of weapons to eliminate pathogens. In DM, neutrophil functions become dysregulated [3, 4]. Many of these functions have been studied in DM; however, a novel function, termed neutrophil swarming, has only recently begun to be characterized. In swarming, neutrophils organize a collective response against a target that may not otherwise be able to be eliminated by individual neutrophils alone. Neutrophil swarming functions in DM have yet to be investigated. We hypothesized that patients with uncontrolled diabetes (defined here as A1C > 10%)) would have defective neutrophil swarming and fungal clearance. To address this knowledge gap, we leveraged a microscale printing assay to target fungal hyphae and elucidate the impacts of diabetes on neutrophil swarming. To do this, 8x8 grids of Poly-l-lysine were printed onto glass slides using a Picospotter (PolyPico, Galway, Ireland) and C. albicans hyphae were attached to each spot. Timelapse microscopy was used to observe neutrophil swarming events in response to these fungal targets. Isolated human neutrophils from healthy individuals were compared to neutrophils from patients with uncontrolled diabetes. We show that most individuals with diabetes have reduced capacity for neutrophil swarming as well as a significant reduction in fungal killing abilities in comparison to healthy controls. Lastly, we show that defective swarm responses of diabetic neutrophils can be rescued with G-CSF (growth-colony stimulating factor) treatment revealing potential therapeutic avenues for patients with diabetes or those who are immunocompromised.
