Chlamydiae Enhance Self-Antigen Presentation in a Mechanism that is Dependent on Biosynthesis of Lipooligosaccharide Public Deposited

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  • Chlamydia is a genus of obligate intracellular bacteria that undergo a unique, biphasic developmental cycle. The infectious and metabolically inert Elementary Bodies (EBs) begin the cycle of infection by attaching and invading a host cells. Once inside, the EBs differentiate into the metabolically active, dividing Reticulate Bodies (RBs) within their own cellular compartment. A significant portion of the chlamydial developmental cycle takes place within the host cell, which presents a challenge for the host immune system to detect and clear the infection. MHC Class I antigen presentation is the adaptive immune system’s answer to this problem by displaying both host and parasitic antigens, if present, to other cells such as CD8⁺ cytotoxic T cells. Previous research has identified chlamydial interactions with host-cell metabolism such as alteration of host transcription and translation. Other previous work has identified chlamydial antigens displayed in MHC Class I molecules. This body of work is the first to describe the impact of Chlamydia spp. infection on MHC Class I self-antigen presentation by enhancing presentation of peptides derived from defective ribosomal products (DRiPs). We hypothesize that enhancing self-antigen presentation is a novel immune evasion strategy by which Chlamyidae saturate MHC Class I molecules with self-antigen and therefore decrease the likelihood that chlamydial antigens are presented. Mechanisms of pathogenesis have often been used to elucidate host molecular pathways such as herpesvirus and the MHC Class I and MHC Class II antigen presentation pathways. The DRiPs pathway is currently unknown, and future endeavors will aim to utilize chlamydial infection to discover the molecular mechanisms of the DRiPs pathway. Additionally, we used a small molecule inhibitor of chlamydial lipooligosaccharide biosynthesis and identified the sensitivities of C. trachomatis L2, C. trachomatis J6276, C. muridarum, C. caviae, and C. suis to the drug. Treatment of infected cells with the inhibitor of LOS resulted in aberrant inclusions in some, but not all species as well as a differential effect on output of infectious EBs. Future experiments will seek to validate the use of the LOS inhibitor as an agent of selection in chlamydial recombination.
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