Event date:
May
17
2021
2:30 pm
Neutrophil release exosomes during phagocytosis, induce NETosis from resting neutrophils
Supervisor
Dr. Shaper Mirza
Student
Iqra Anam Ranjha
Venue
Zoom Meetings (Online)
Event
MS Thesis defense
Abstract
Diabetes is one of a major health problem worldwide. Hyperglycemia results in aberrant functioning of immune system which fails to control the pathogenic spread in body. The abnormal immune cells in both innate and adaptive immunity are potential reasons to increase the diabetic susceptibility. Diabetes is associated with several neutrophilic impairments, which leads to higher prevalence of bacterial infections. Such impairments include killing of pathogens, production of ROS, downstream phagocytosis, and translocation. Neutrophils are associated with killing of pathogen both intracellularly and extracellularly i-e phagocytosis and NETosis. Furthermore, recent studies have revealed that NET formation is mediated by autophagy. Autophagy and phagocytosis occurred simultaneously in cellular environment; however, the mechanism remains to be elucidated.
Exosomes are produced from neutrophils during phagocytosis, which are small intact vesicles ranging from 30-500nm size. Upon stimulation, neutrophils released exosomes into the media. Exosomes are capable of penetrating membranes of neighboring cells. Inherently, exosomes are antigen presenting vesicles, having specific protein markers on their surfaces. Therefore, by presenting specific markers on their surfaces, exosomes induce phagocytosis in neighboring neutrophils.
While exosomes and TLRs are two independent molecules, many studies revealed that exosomes regulate innate immunity through interacting with TLRs on surface of neutrophils. The mechanism of interaction is unclear. Toll like receptors (TLR’s) are linked with increase in ROS production. Since ROS also play an integral role in induction and expression of NETs, we wanted to determine if ROS produced by the engagement of TLR with exosomes, initiate intracellular processes required for NETs expression. To understand the role of exosomes we purpose to investigate the impact of exosomes on induction and release of NETs. Our results indicated that exosomes isolated from neutrophils in the presence of S. pneumoniae were able to induce NETs in resting neutrophils. A thorough understanding of the processes of isolation and analysis research could lead to some standardization in the field of exosomal research, allowing the use of exosomes in the clinical setting to become a reality.
Exosomes are produced from neutrophils during phagocytosis, which are small intact vesicles ranging from 30-500nm size. Upon stimulation, neutrophils released exosomes into the media. Exosomes are capable of penetrating membranes of neighboring cells. Inherently, exosomes are antigen presenting vesicles, having specific protein markers on their surfaces. Therefore, by presenting specific markers on their surfaces, exosomes induce phagocytosis in neighboring neutrophils.
While exosomes and TLRs are two independent molecules, many studies revealed that exosomes regulate innate immunity through interacting with TLRs on surface of neutrophils. The mechanism of interaction is unclear. Toll like receptors (TLR’s) are linked with increase in ROS production. Since ROS also play an integral role in induction and expression of NETs, we wanted to determine if ROS produced by the engagement of TLR with exosomes, initiate intracellular processes required for NETs expression. To understand the role of exosomes we purpose to investigate the impact of exosomes on induction and release of NETs. Our results indicated that exosomes isolated from neutrophils in the presence of S. pneumoniae were able to induce NETs in resting neutrophils. A thorough understanding of the processes of isolation and analysis research could lead to some standardization in the field of exosomal research, allowing the use of exosomes in the clinical setting to become a reality.
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Meeting ID: 980 4953 5107
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