UC Riverside

Vector-borne diseases have a major impact in mortality and morbidity throughout the tropics. Vector-borne pathogens are transmitted to humans by blood feeding arthropods like mosquitoes and ticks. A true understanding of the vector-borne disease cycle requires the study of the major players involved in this cycle: the mammalian host, the pathogen and the arthropod vector. This thesis examines these aspects by using a tick-borne disease, human granulocytic anaplasmosis (HGA), as a model. Chapters 1, 2 and 3 emphasize the importance of vector-borne diseases and discuss medically relevant arthropod vectors in light of their immune response to human pathogens. The etiologic agent of HGA, Anaplasma phagocytophilum, is also examined in detail, with a focus on immune evasion strategies used to colonize mammals and ticks. Chapters 4 thru 6 are dedicated to address pathogen, host and the tick vector, respectively. First, the contribution of one A. phagocytophilum gene, the dihydrolipoamide dehydrogenase, to infection is demonstrated. Next, the role of tick saliva as an immunomodulator of A. phagocytophilum infection in the mammalian host is revealed. Finally, an Ixodes scapularis X-linked inhibitor of apoptosis protein is described as an E3 ubiquitin ligase that controls tick colonization by A. phagocytophilum. In summary, this dissertation uncovers three distinct events underlying the tick-pathogen-host interface.