Bacterial species of the genus Neisseria include pathogens that are responsible for diseases of humans including bacterial meningitis (Neisseria meningitidis) and the sexually transmitted disease gonorrhea (Neisseria gonorrhoeae). These diseases are often characterized by a massive influx and activation of neutrophils, white blood cells involved in the early/innate immune response to pathogens, at the infection site. Neisseria spp. bind to and activate neutrophils via their Opacity-associated (Opa) outer membrane proteins, which interact with some members of the human carcinoembryonic antigen-related cellular adhesion molecule (CEACAM) family. One of these CEACAMs, CEACAM3 (CD66d), is unique in its restriction to neutrophils and its expression of a cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM; YxxL/Ix6-8YxxL/I). In the course of my thesis work, I have shown that this motif is critically dependent for the activation of the neutrophil response to Neisseria, through the coupling of neisserial binding to activation of the tyrosine kinase, Syk, which initiates downstream signaling responsible for the antimicrobial responses of neutrophils. These data contribute to the knowledge of how seemingly unrelated receptors of neutrophils (such as the IgG-binding Fcγ receptors, the fungal receptor Dectin-1, and the bacterial-binding CEACAM3) converge functionally on the presence of the ITAM.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/17829 |
| Date | 28 September 2009 |
| Creators | Sarantis, Helen |
| Contributors | Gray-Owen, Scott |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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