Document Type
Poster Session
Department
Biomedical Science and Engineering
Faculty Mentor
Catherine Miller
Keywords
Neutrophils, Neutrophil NETs, Neutropenia
Abstract
Neutrophils, also called polymorphonuclear leukocytes (PMNs), constitute the majority of innate immune cells. These cells possess a complex arsenal of functions that allow them to detect and eliminate a broad spectrum of pathogens. Neutropenia is characterized by decreased levels of neutrophils in the bloodstream, typically falling below the normal range. Moderate to severe neutropenia can increase the risk of pathogenic infections and without treatment can be life-threatening. Although the concentration of neutrophils in neutropenic individuals is decreased, upon activation, neutrophils still release neutrophil extracellular traps (NETs). NETs are pivotal in combating a spectrum of pathogens through their non-selective nature. Overreactive NET production can inadvertently harm surrounding tissues and cause more tissue damage. This indiscriminate action is connected to conditions like psoriasis, rheumatoid arthritis, and autoinflammatory diseases. Targeting NETs presents a potential therapeutic avenue to decrease disease severity. Suicidal NETs, a sub-variant of NETs, often worsen tissue damage by compromising neutrophil integrity. Conversely, vital NETs offer a more controlled outcome, allowing for less tissue damage and a longer survivability. Understanding the balance between these NET subtypes is critical for devising targeted interventions for neutropenic individuals. This study addresses the hypothesis that neutrophils from neutropenic individuals produce a larger quantity of vital NETs in response to common pathogenic bacterial strains. This heightened overproduction of vital NETs in response to bacterial pathogens is thought to serve as a compensatory mechanism in the context of diminished neutrophil levels. Neutrophils were collected from both healthy individuals and those with neutropenia. To selectively induce the production of vital NETs, a kinase inhibitor was used to suppress the production of suicidal NETs. Following this inhibition, the neutrophils were exposed to bacterial stimulation to trigger the production of vital NETs. Finally, the NETs were visualized using fluorescence microscopy after staining with DNA-specific dyes for visualization. This study indicates that neutropenic individuals may exhibit an overproduction of vital NETs.
Included in
Biotechnology Commons, Cell and Developmental Biology Commons, Immune System Diseases Commons, Immunology and Infectious Disease Commons, Pathogenic Microbiology Commons
Investigating Vital Neutrophil Extracellular Trap Pathogen Response in Neutropenic Individuals
Neutrophils, also called polymorphonuclear leukocytes (PMNs), constitute the majority of innate immune cells. These cells possess a complex arsenal of functions that allow them to detect and eliminate a broad spectrum of pathogens. Neutropenia is characterized by decreased levels of neutrophils in the bloodstream, typically falling below the normal range. Moderate to severe neutropenia can increase the risk of pathogenic infections and without treatment can be life-threatening. Although the concentration of neutrophils in neutropenic individuals is decreased, upon activation, neutrophils still release neutrophil extracellular traps (NETs). NETs are pivotal in combating a spectrum of pathogens through their non-selective nature. Overreactive NET production can inadvertently harm surrounding tissues and cause more tissue damage. This indiscriminate action is connected to conditions like psoriasis, rheumatoid arthritis, and autoinflammatory diseases. Targeting NETs presents a potential therapeutic avenue to decrease disease severity. Suicidal NETs, a sub-variant of NETs, often worsen tissue damage by compromising neutrophil integrity. Conversely, vital NETs offer a more controlled outcome, allowing for less tissue damage and a longer survivability. Understanding the balance between these NET subtypes is critical for devising targeted interventions for neutropenic individuals. This study addresses the hypothesis that neutrophils from neutropenic individuals produce a larger quantity of vital NETs in response to common pathogenic bacterial strains. This heightened overproduction of vital NETs in response to bacterial pathogens is thought to serve as a compensatory mechanism in the context of diminished neutrophil levels. Neutrophils were collected from both healthy individuals and those with neutropenia. To selectively induce the production of vital NETs, a kinase inhibitor was used to suppress the production of suicidal NETs. Following this inhibition, the neutrophils were exposed to bacterial stimulation to trigger the production of vital NETs. Finally, the NETs were visualized using fluorescence microscopy after staining with DNA-specific dyes for visualization. This study indicates that neutropenic individuals may exhibit an overproduction of vital NETs.
