<I>Chlamydia trachomatis</I> (CT) is an obligate intracellular bacteria and is a common cause of ocular and genital infections in human populations. Murine models of CT infection have shown that Natural Killer cells (NK cells) are recruited into the genital tract early after infection, and are an important source of the cytokine IFN-γ. NK cells are part of the innate defences against infection through cytokine production (IFN-γ, TNF-α and GM-CSF) and cytolytic activity. The hypothesis investigated in this thesis was that CT-infection of target cells leads to alterations in the target cell that are recognized by NK cells, activating one or more of their effector functions. Cervical epithelial tumour lines (HeLa and SiHa) were infected with CT and used as targets in cytotoxicity assays, with polyclonal NK cell lines from healthy individuals as the effector cells. It was found that the level of lysis was significantly raised when CT-infected targets were compared to mock-infected controls. UV-inactivated CT did not induce this increase in lysis, and inhibiting CT-protein synthesis also abolished the effect of live infection. Primary human fibroblasts were not lysed significantly following infection. Investigation of the expression NK cell ligands following CT infection revealed reductions in Classical Class I MHC and HLA-E levels on infected cells. This reduction was seen on both the epithelial cell lines and the primary fibroblasts. The different susceptibility to NK cells is likely to be the consequence of expression of different activatory ligands by the different target cells. Cytokine production by the NK cells following exposure to supernatants from CT-infected cells was assessed and it was shown that supernatants from CT-infected HeLa cells could, in conjunction with rhIL-12, induce NK cell IFN-γ production. Supernatants from CT-infected dendritic cells (DCs) were found to induce NK cell IFN-γ production in conjunction with rhIL-18. This thesis provides evidence for interactions between CT-infected cells and Human NK cells; both cell contact-dependent and soluble mediator-dependent interactions have been demonstrated. Thus, mechanisms have been elucidated via which human NK cells could play an important role in the innate defences against CT infection.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:604208 |
| Date | January 2002 |
| Creators | Hook, C. E. |
| Publisher | University of Cambridge |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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