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Title: Immune regulation of Chlamydia psittaci persistence in sheep
Author: Brown, Jeremy Keith
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1999
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Chlamydia psittaci is the causative agent of ovine enzootic abortion (OEA), the single most common cause of diagnosed infectious ovine abortion in the United Kingdom. Diagnosis and control of OEA is complicated by the ability of C. psittaci to establish a chronic low level or persistent infection in ewes infected out-with pregnancy. Persistent C. psittaci infection was reproduced in vitro by maintaining infected ovine fibroblastic ST.6 cells in the presence of recombinant ovine interferon gamma (ROvIFN-γ) at physiologically relevant concentrations for up to 63 days after infection. ROvIFN-γ restricted C. psittaci growth in a dose dependent manner, concentrations of 25-100 units of biological activity per millilitre (U/ml) induced and maintained persistence whereas concentrations of 250 U/ml or more eradicated C. psittaci from infected cultures. Attempts to identify and characterise the source of IFN-γ in immune sheep using T-cell lines raised against recombinant C. psittaci proteins were unsuccessful. The mechanisms of ROvIFN-γ mediated restriction of C. psittaci were investigated. Pretreatment of ST.6 cells with recombinant interferon alpha or double stranded RNA at concentrations matched with ROvIFN-γ for anti-viral activity did not restrict C. psittaci growth in ST.6 cells, indicating that the mechanism through which ROvIFN-γ restricts C. psittaci in ovine cells is independent from its anti-viral activities. Nitric oxide was not detected in the supernates of infected ST.6 cells pretrated with ROvIFN-γ and addition of L-NMMA, a potent inhibitor of inducible nitric oxide synthase, did not alter the anti- C. psittaci effects of ROvIFN-γ in this cell line. Furthermore, nitric oxide production could not be demonstrated in primary ovine alveolar macrophages treated with combinations of ROvIFN-γ, LPS, heat inactivated C. psittaci and/or live C. psittaci. Addition of exogenous L-tryptophan partially reversed the anti-chlamydial effects of ROvIFN-γ in ST.6 cells that had been infected with C. psittaci over a 48 hours period and also resulted in the recovery of infectious Chlamydiae from persistently infected ST.6 cells maintained in 50 U/ml of ROvIFN-γ. These findings support a role for up-regulation of tryptophan catabolism in ROvIFN-γ mediated restriction of both C. psittaci growth and persistence in ovine cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available