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dc.contributor.advisorBrown, Wendy
dc.creatorMudenda, Lwiindi
dc.date.accessioned2015-11-02T19:09:05Z
dc.date.available2015-11-02T19:09:05Z
dc.date.issued2015
dc.identifier.urihttp://hdl.handle.net/2376/5469
dc.descriptionThesis (Ph.D.), College of Veterinary Medicine, Washington State Universityen_US
dc.description.abstractTicks are obligate blood sucking parasites which transmit a wide range of pathogens worldwide including protozoa, bacteria and viruses. Additionally, tick feeding alone may result in anemia, dermatosis and toxin-induced paralysis. Dermacentor andersoni is a species of tick found in the western United States that transmits pathogens of public health importance including Rickettsia rickettsii, Francisella tularensis, and Colorado Tick Fever Virus, as well as Anaplasma marginale, a rickettsial pathogen that causes economic losses in both the dairy and beef industries worldwide. D. andersoni ticks are obligate blood sucking parasites that require a blood meal through all stages of their lifecycle. During feeding, ticks secrete factors that modulate both innate and acquired immune responses in the host which enables them to feed for several days without detection. The pathogens transmitted by ticks exploit these immunomodulatory properties to facilitate invasion of and replication in the host. Molecular characterization of these immunomodulatory proteins secreted in tick saliva offers an opportunity to develop novel anti-tick vaccines as well as anti-inflammatory drug targets. To this end we performed deep sequence analysis on unfed ticks and ticks fed for 2 or 5 days. The pooled data generated a database of 21,797 consensus sequences. Salivary gland gene expression levels of unfed ticks were compared to 2- and 5-day fed ticks to identify genes upregulated early during tick feeding. Next we performed mass spectrometry on saliva from 2- and 5-day fed ticks and used the database to identify 677 proteins. We cross referenced the protein data with the transcriptome data to identify 157 proteins of interest for immunomodulation and blood feeding. Both proteins of unknown function and known immunomodulators were identified. We expressed four of these proteins and tested them for inhibition of macrophage activation and/or cytokine expression in vitro. The results showed diverse effects of the various test proteins on the inflammatory response of mouse macrophage cell lines. The proteins upregulated some cytokines while downregulating others. However, all the proteins upregulated the regulatory cytokine IL-10.en_US
dc.description.sponsorshipCollege of Veterinary Medicine, Washington State Universityen_US
dc.language.isoEnglish
dc.rightsIn copyright
dc.rightsPublicly accessible
dc.rightsopenAccess
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/
dc.rights.urihttp://www.ndltd.org/standards/metadata
dc.rights.urihttp://purl.org/eprint/accessRights/OpenAccess
dc.subjectImmunologyen_US
dc.subjectMolecular biologyen_US
dc.subjectBioinformaticsen_US
dc.subjectGene expressionen_US
dc.subjectMass spectrometryen_US
dc.subjectProteomicsen_US
dc.subjectSaliva proteinsen_US
dc.subjectTicken_US
dc.subjectTranscriptomicsen_US
dc.titleIdentification of Dermacentor andersoni saliva proteins that modulate mammalian phagocyte function
dc.typeElectronic Thesis or Dissertation


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