African trypanosomiasis is once again a major public health problem throughout much of Africa. Control strategies are limited due to the lack of mammalian vaccines and efficacious and affordable drugs. The recent developments in recombinant DNA technologies stand to improve existing vector control measures, but progress in this are has been hampered by the lack of information on the molecular aspects of tsetse and its interactions with trypanosomes. Tsetse flies are in general refractory to the transmission of African trypanosomes although the molecular basis for refractoriness is unknown. Pdor induction of the tsetse immune system can reduce parasite transmission indicating that tsetse's innate defense surveillance system is capable of terminating the development of trypanosomes. In the work proposed here, a comprehensive panel of immune-responsive genes will be identified using several different molecular strategies and their expression profiles in response to different immune challenges will be analyzed. Both systemic and local responses, respectively mediated by fat body and proventriculus tissue, will be investigated at the molecular level. Functional studies are proposed with several key antimicrobial gene products to understand their role in parasite transmission. This study will allow us to begin to understand the components of the tsetse immune system and the interactions they exhibit with trypanosomes during the parasite establishment and transmission in the fly. Although germ line transformation approach is difficult in tsetse because of its unusual reproductive biology, expression of transgenes in the gut symbionts of tsetse, particularly Sodalis glossinidius, may prove a valuable strategy to control disease transmission. Central to such a strategy will be identification of suitable genes for use as transgenes. Immunity genes are strong =candidates which this study may help to identify. These genes may also play a role in differentiation of trypanosomes and again, this project will identify potential candidates.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI051584-05
Application #
7148695
Study Section
Special Emphasis Panel (ZRG1-TMP (01))
Program Officer
Costero, Adriana
Project Start
2002-12-15
Project End
2008-11-30
Budget Start
2006-12-01
Budget End
2008-11-30
Support Year
5
Fiscal Year
2007
Total Cost
$387,569
Indirect Cost
Name
Yale University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Vigneron, Aurélien; Aksoy, Emre; Weiss, Brian L et al. (2018) A fine-tuned vector-parasite dialogue in tsetse's cardia determines peritrophic matrix integrity and trypanosome transmission success. PLoS Pathog 14:e1006972
Awuoche, Erick O; Weiss, Brian L; Mireji, Paul O et al. (2018) Expression profiling of Trypanosoma congolense genes during development in the tsetse fly vector Glossina morsitans morsitans. Parasit Vectors 11:380
Griffith, Bridget C; Weiss, Brian L; Aksoy, Emre et al. (2018) Analysis of the gut-specific microbiome from field-captured tsetse flies, and its potential relevance to host trypanosome vector competence. BMC Microbiol 18:146
Zaidman-Rémy, Anna; Vigneron, Aurélien; Weiss, Brian L et al. (2018) What can a weevil teach a fly, and reciprocally? Interaction of host immune systems with endosymbionts in Glossina and Sitophilus. BMC Microbiol 18:150
Benoit, Joshua B; Vigneron, Aurélien; Broderick, Nichole A et al. (2017) Symbiont-induced odorant binding proteins mediate insect host hematopoiesis. Elife 6:
Bateta, Rosemary; Wang, Jingwen; Wu, Yineng et al. (2017) Tsetse fly (Glossina pallidipes) midgut responses to Trypanosoma brucei challenge. Parasit Vectors 10:614
Awuoche, Erick O; Weiss, Brian L; Vigneron, Aurélien et al. (2017) Molecular characterization of tsetse's proboscis and its response to Trypanosoma congolense infection. PLoS Negl Trop Dis 11:e0006057
Savage, Amy F; Kolev, Nikolay G; Franklin, Joseph B et al. (2016) Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans. PLoS One 11:e0168877
Aksoy, Emre; Vigneron, Aurélien; Bing, XiaoLi et al. (2016) Mammalian African trypanosome VSG coat enhances tsetse's vector competence. Proc Natl Acad Sci U S A 113:6961-6
Zhao, Xin; Alves e Silva, Thiago Luiz; Cronin, Laura et al. (2015) Immunogenicity and Serological Cross-Reactivity of Saliva Proteins among Different Tsetse Species. PLoS Negl Trop Dis 9:e0004038

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