Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Microbiology and Immunology

Supervisor

Dr. Bryan Heit

Abstract

Every day billions of cells in our bodies undergo apoptosis and are cleared through efferocytosis – a phagocytosis-like process in which phagocytes engulf and degrade apoptotic cells. Proper processing of efferosomes prevents inflammation and immunogenic presentation of antigens. In this thesis I determined that the early stages of efferosome maturation parallel that of the pro-immunogenic phagocytosis of pathogens. Mass spectrometry analysis of later maturation stages identified unique regulatory proteins on efferosomes and phagosomes. Keys among these were Rab17 and Rab45 on efferosomes versus Rab6b and PI-4-Kinase on phagosomes. The later would allow for antigen presentation from phagosomes, while the former would direct efferosome-derived antigens away from this presentation pathway. Moreover, positive regulators of MAP-kinase signaling were enriched on phagosomes, while negative regulators were enriched on efferosomes, perhaps indicating the mechanism through which efferocytosis inhibits inflammation. These regulators may account for the differences in inflammation and immunogenicity observed after efferocytosis versus phagocytosis.


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