Immune mechanisms operating in mosquitoes are capable of limiting or preventing the development of filarial worms within these vectors. Although melanotic encapsulation reactions are responsible for resistance in certain species of mosquitoes, parasites are often capable of developing in other closely related species or even other strains, of the same species. Why certain mosquito species respond effectively while others do not, or why a species can immunologically destroy one parasite species but not another, are questions of fundamental relevance to our understanding of vector-parasite compatibility. The objective of the proposed research is to elucidate immune recognition and effector mechanisms and their regulation in mosquitoes exposed to filarial worms. Various biochemical and molecular techniques will be used with the mosquitoes Aedes aegypti, Aedes trivittatus and the filarial worms Brugia malayi, B. pahangi and Dirofilaria immitis (1) quantitatively assess the role specific enzymes and substrates might play in the production of protein-polyphenol complexes required for the immune destruction of microfilariae in mosquitoes, (2) identify and characterize hemolymph proteins that are uniquely or preferentially expressed in mosquitoes during melanotic encapsulation reactions, (3) characterize functional differences in mosquito hemocytes using lectins and anti-hemocyte monoclonal antibodies, and (4) begin characterizing immune mechanisms operating in the Armigeres subalbatus-Brugia spp. vector-parasite system that allows the development of B. pahangi but results in the immune destruction of B. malayi. The proposed studies will provide an increased clarification of mechanisms of immune responses in mosquitoes and a greater insight into vector-parasite associations, thereby increasing our understanding of the epidemiology of mosquito-borne filariasis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI019769-11
Application #
3481070
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1983-04-01
Project End
1995-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
11
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Earth Sciences/Natur
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Choi, Young-Jun; Aliota, Matthew T; Mayhew, George F et al. (2014) Dual RNA-seq of parasite and host reveals gene expression dynamics during filarial worm-mosquito interactions. PLoS Negl Trop Dis 8:e2905
Liu, Pingyang; Torrens-Spence, Michael P; Ding, Haizhen et al. (2013) Mechanism of cysteine-dependent inactivation of aspartate/glutamate/cysteine sulfinic acid ?-decarboxylases. Amino Acids 44:391-404
Choi, Young-Jun; Fuchs, Jeremy F; Mayhew, George F et al. (2012) Tissue-enriched expression profiles in Aedes aegypti identify hemocyte-specific transcriptome responses to infection. Insect Biochem Mol Biol 42:729-38
Liu, Pingyang; Ding, Haizhen; Christensen, Bruce M et al. (2012) Cysteine sulfinic acid decarboxylase activity of Aedes aegypti aspartate 1-decarboxylase: the structural basis of its substrate selectivity. Insect Biochem Mol Biol 42:396-403
Liu, Pingyang; Ge, Xiaomei; Ding, Haizhen et al. (2012) Role of glutamate decarboxylase-like protein 1 (GADL1) in taurine biosynthesis. J Biol Chem 287:40898-906
Han, Qian; Robinson, Howard; Ding, Haizhen et al. (2012) Evolution of insect arylalkylamine N-acetyltransferases: structural evidence from the yellow fever mosquito, Aedes aegypti. Proc Natl Acad Sci U S A 109:11669-74
Mehere, Prajwalini; Han, Qian; Christensen, Bruce M et al. (2011) Identification and characterization of two arylalkylamine N-acetyltransferases in the yellow fever mosquito, Aedes aegypti. Insect Biochem Mol Biol 41:707-14
Choi, Young-Jun; Ghedin, Elodie; Berriman, Matthew et al. (2011) A deep sequencing approach to comparatively analyze the transcriptome of lifecycle stages of the filarial worm, Brugia malayi. PLoS Negl Trop Dis 5:e1409
Vavricka, Christopher; Han, Qian; Huang, Yongping et al. (2011) From L-dopa to dihydroxyphenylacetaldehyde: a toxic biochemical pathway plays a vital physiological function in insects. PLoS One 6:e16124
Aliota, Matthew T; Chen, Cheng-Chen; Dagoro, Henry et al. (2011) Filarial worms reduce Plasmodium infectivity in mosquitoes. PLoS Negl Trop Dis 5:e963

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