Pathogenic Neisseria infections of human neutrophils and epithelial cells: focusing on host responses and immune evasion
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
N. meningitidis and N. gonorrhoeae are obligate human pathogens that colonize mucosal surfaces and are often carried asymptomatically. These bacteria have developed adhesive structures that promote adherence to host cells and efficient colonization of new hosts. N. gonorrhoeae causes the sexually transmitted disease gonorrhea, which remains one of the most common sexually transmitted diseases, despite the availability of effective antibiotic treatments. N. meningitidis is frequently found in the nasopharynx of healthy individuals as a part of the normal microbiota. However, this bacterial species is a major cause of mortality when it causes septicemia and epidemic meningitidis. The design of vaccines conferring protection against multiple serogroups is difficult; this fact, combined with increased global resistance to antibiotics, emphasizes the need for a better understanding of the pathogenesis of these species. The aim of this thesis was to study the effects of bacterial adherence to human neutrophils (PMNs) and epithelial cells. The adherence of N. meningitidis and N. gonorrhoeae to primary PMNs was investigated in Paper I. Specific adherence of the bacteria to the PMN uropod was observed. By adhering to the uropod, the bacteria could avoid phagocytosis and use the migrating PMNs for transportation. The type IV pilus, which is a known bacterial adhesin, was found to promote uropod adherence. In Paper II, adherence of N. gonorrhoeae to non-polarized cervical and vaginal epithelial cells was found to cause DNA damage and delay cell cycle progression. Upregulation and nuclear localization of the cyclin-dependent kinase inhibitors p21 and p27 were observed, which could contribute to reduced cell proliferation. Interestingly, the levels of tumor suppressing protein 53 (TP53) were affected by bacterial colonization in a non-tumor cell line. In Paper III, colonization by Lactobacillus spp. was found to induce the accumulation of host cells in G1 phase and the upregulation of p21. The adherence of N. gonorrhoeae to polarized epithelial cells and the impact of PMN presence were investigated in Paper IV. N. gonorrhoeae adherence to polarized epithelial cells was significantly higher than adherence to non polarized cells. Cell culture medium containing degranulated products from stimulated PMNs was found to promote bacterial adherence. Finally, PMNs with bacteria adhered to the uropod were able to transport the bacteria through a polarized cell layer. In summary, this thesis investigates the impact of adhesion of pathogenic Neisseria spp. to host epithelial cells and PMNs.
Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , 2013. , 59 p.
Neisseria meningitidis, Neisseria gonorrhoeae, Neutrophils, PMN, Epithelial cells, Polarized cells, Type IV pili, Adherence, Cell cycle, DNA damage, Lactobacillus
Research subject Molecular Bioscience
IdentifiersURN: urn:nbn:se:su:diva-92446ISBN: 978-91-7447-725-2OAI: oai:DiVA.org:su-92446DiVA: diva2:639184
2013-09-06, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
Rudel, Thomas, Professor
Aro, Helena, Assoc. Prof.
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.2013-08-152013-08-052013-08-13Bibliographically approved
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