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Title: The potential role of Wolbachia as a defensive mutualist in the Onchocerca ochengi nodule
Author: Hansen, Rowena Dawn Ellen
ISNI:       0000 0004 2737 7107
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2011
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Onchocerciasis (River Blindness) is a continuing major cause of human blindness, skin disease and socioeconomic impediment in sub-Saharan Africa and Latin America. An estimated 37 million people are infected and a further 89 million are at risk. Human onchocerciasis is caused by the filarial nematode Onchocerca volvulus, and is spread by the blackfly vector Simulium spp, found in riverine areas, encompassing land which is agriculturally valuable. Ivermectin is currently distributed in these areas to control the microfilarial stage of the parasite, but adult worm viability is unaffected. Thus, due to the long lifespan of the worms (>10 years), treatment regimens must be continued for many years. Furthermore, there are signs that ivermectin resistance is emerging. The bovine filarial parasite Onchocerca ochengi represents the closest phylogenetic relative of 0. volvulus. In both species, female worms reside in nodules, and continue to reproduce for many years whilst surrounded by a milieu of host inflammatory cells and antibodies. In addition, both species harbour endosymbiotic bacteria (Wolbachia) which are essential for worm survival. Although a metabolic role for these bacteria has been hypothesised, the symbiotic mechanisms between filariae and Wolbachia are not fully understood. In the filarial nodule, neutrophils are attracted to Wolbachia-rich worms, but if the bacteria are depleted via antibiotic chemotherapy, the neutrophils are replaced by eosinophils that degranulate on the worm cuticle. However, the specific contribution of eosinophils towards filarial death is unresolved. This study sought to define the role of eosinophils in either the active killing or post-killing clearance of Wolbachia-depleted filariae. In an in-vivo longitudinal study of 0. ochengi- infected cattle receiving adulticidal regimens of oxytetracycline or melarsomine, histopathological analysis of nodules revealed a switch from neutrophils to eosinophils in oxytetracycline-treated animals, but not following melarsomine treatment, and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) demonstrated that viable Wolbachia were depleted only by oxytetracycline chemotherapy. Eosinophil degranulation increased significantly only in the oxytetracycline group; whereas nodular gene expression of bovine neutrophilic chemokines was lowest in this group. Moreover, intense eosinophil degranulation was initially associated with worm vitality, not degeneration, while transmission electron microscopy (TEM) revealed subsequent cuticular damage in Wolbachia-depleted worms. Taken together, these data offer strong support for the hypothesis that Wolbachia confers longevity on 0. ochengi through a defensive mutualism, in which neutrophils attracted to Wolbachia divert a potentially lethal effector response by eosinophils.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral