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Functional characterization of Glossina morsitans morsitans saliva in the context of African trypanosome transmission

Wednesday, 20 December, 2006 - 14:00
Campus: Brussels Humanities, Sciences & Engineering campus
Faculty: Science and Bio-engineering Sciences
D
2.01
Guy Caljon
phd defence

Tsetse flies are important disease vectors, responsible for the transmission of African
trypanosomes causing human sleeping sickness and veterinary infections in the African
continent. During the obligate bloodfeeding interaction, tsetse flies deposit a complex salivary
mixture that might inhibit host defences and support efficient trypanosome transmission. As
such, this PhD primarily assessed immunological and molecular aspects of the tsetse fly/host
interaction.

Immunological analyses demonstrated that the major 43-45 kDa protein fraction (tsetse
salivary gland protein 1 and 2 - Tsal1 and Tsal2) of Glossina morsitans morsitans saliva
induces strong humoral responses in mice and humans. Using prokaryotic expressed Tsal1
and Tsal2, an immunological assay for human tsetse fly exposure was tested and found
applicable for eventual epidemiological surveys. Additional analysis revealed that saliva
exposure in mice results in a Th2 biased cytokine profile and associated IgG1 and IgE
antibody production. These antibody responses did not affect the fly’s blood feeding
efficiency nor its survival, suggesting that tsetse flies might prevent the outcome of
detrimental anti-vector immune responses. Supporting this hypothesis, reduced murine T and
B cell responses were recorded in co-immunization experiments against heterologous
antigens.

Infection experiments additionally demonstrated that tsetse fly saliva accelerates a
Trypanosoma brucei infection onset, associated with reduced local inflammation and
diminished systemic production of the trypanocidal cytokine TNF. Surprisingly, a history of
repeated tsetse fly exposure also enhances trypanosome expansion in the early infection
phase.

To unravel the tsetse salivary composition, a G. m. morsitans λgt11 salivary gland expression
library was generated and subjected to immune screening. Using this approach, full length
cDNA clones encoding three unknown secreted salivary components were identified. In
addition, detailed in silico analysis revealed significant homology for Tsal1 and Tsal2 with
the CD39 “apyrase conserved region 1” (ACR1) and the shrimp Marsupenaeus japonicus
nuclease. Eukaryotic protein expression, activity analysis and in vivo RNA interference,
functionally characterized Tsal1 and Tsal2 as representatives of a novel class of salivary
enzymes in bloodfeeding insects with combined apyrase and nuclease activities. Collectively,
this research offered new insights in the tsetse/host-interaction and trypanosome transmission.