Type
Text
Type
Dissertation
Advisor
Cutler, Christopher W. | David G. Thanassi | Michael Hayman | Adrianus W.M. Van der Velden | Caroline A. Genco.
Date
2010-12-01
Keywords
DC-SIGN, Dendritic Cells, Glycosylation, Immuno-modulation, Innate Immunity, Porphyromonas gingivalis | Microbiology -- Immunology -- Biology
Department
Department of Molecular Genetics and Microbiology
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/72726
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
The broad objective of this dissertation is to elucidate the specific interactions between Porphyromonas gingivalis (P. gingivalis) and dendritic cells (DCs). P. gingivalis is a black pigmented, anaerobic, Gram-negative bacterium that is associated with most cases of chronic periodontitis. P. gingivalis expresses a myriad of virulence factors, most notably, fimbrial adhesins that enable it to bind to and invade host epithelial cells, endothelial cells, macrophages and DCs. While much is known about the 41 kDa major fimbria adhesins of P. gingivalis, the minor fimbriae have received little attention. The results presented here suggest that the minor fimbriae may serve as an immunosuppressive factor, by targeting the C-type lectin receptor DC-SIGN. DC-SIGN (CD209) is involved in uptake of certain pathogens by DC, in the formation of DC-T cell conjugates, and is increasingly expressed in chronic periodontitis (CP) lesions. Targeting DC-SIGN for entry into DCs has proved an effective immuno-evasive strategy for certain pathogens. DC-SIGN ligation down-modulates maturation of DCs, dampens DC secretion of pro-inflammatory and Th1-cytokines necessary for induction of protective immunity and, possibly, compromises intracellular killing mechanisms. The aim for this research was to investigate the role of the minor fimbriae of P. gingivalis in invasion of DC's and in activation of immunosuppressive innate signaling pathways. I determined that the minor fimbriae targets DC-SIGN on DCs. Furthermore, I discovered that the minor fimbriae are glycosylated with DC-SIGN targeting sugars (fucose, mannose, galactose, and N-acetylglucosamine). Detection of glycosylation was determined using endoglycosidases and then confirmed via gas chromatography-mass spectrometry (GC-MS). Finally, it was determined that minor fimbriae targeting of DC-SIGN has an immunosuppressive effect on DCs as well as on T cells co-cultured with pulsed DCs.
Recommended Citation
Zeituni, Amir Emanuel, "The specific interactions between dendritic cells and Porphyromonas gingivalis" (2010). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 1929.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/1929