Approximately 120 million individuals are infected with Schistosoma haematobium in sub-Saharan African alone. S. haematobium adult worms, the causative agent of urogenital schistosomiasis, lay eggs throughout the urogenital tract. These eggs induce a pronounced inflammatory response responsible for the human morbidity and mortality associated with infection. To date very little is known about how S. haematobium is able to induce such a robust immune response while evading immune clearance and immunity in many individuals. This lack of knowledge is due to the historical lack of both a model for S. haematobium egg- associated pathology, and genetic tools for manipulation of the S. haematobium parasite. Building on recent advances in the S. haematobium field, this collaborative proposal employs the first published mouse model of S. haematobium induced bladder pathology (generated by the PI), and the first successful approaches for genetic manipulation of S. haemtobium (pioneered by the co-investigators). The experiments proposed will explore the functions of the S. haematobium homolog of the parasite egg- secreted immunomodulatory protein IPSE. IPSE was originally described in S. mansoni, the sister species of schistosome responsible for hepatoenteric schistosomiasis. IPSE is the most abundant S. mansoni egg secreted protein, and has numerous published biochemical functions, many of which were first described by a co-investigator on this proposal. Our collaborative team across four institutions will first define the biochemical functions of the S. haematobium IPSE homologue. We will then generate genetically modified S. haematobium strains with deficient IPSE gene expression to determine the effects of IPSE in vivo. Achievement of the aims of this proposal would represent key milestones for S. haematobium research, including, to our knowledge, the first studies on S. haematobium-derived immunomodulatory proteins and the first use of transgenic S. haematobium strains to determine the function of an S. haematobium protein in vivo.

Public Health Relevance

Schistosoma haematobium, the parasitic worm responsible for urogenital schistosomiasis, infects over a hundred million individuals annually. There are few tools available to help researchers understand and prevent this neglected tropical disease. This proposal aims to advance our understanding of S. haematobium immunomodulation during infection, and to generate the first set of tools to allow scientists to study the functions of S. haematobium proteins in vivo.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
High Priority, Short Term Project Award (R56)
Project #
1R56AI119168-01
Application #
9107658
Study Section
Immunity and Host Defense (IHD)
Program Officer
Wali, Tonu M
Project Start
2015-09-01
Project End
2017-08-31
Budget Start
2015-09-01
Budget End
2017-08-31
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Biomedical Research Institute
Department
Type
DUNS #
076137314
City
Rockville
State
MD
Country
United States
Zip Code
20852