The overall objective of this proposal is to prospectively investigate the interrelationships among puberty, protective immune responses, and nutritional status in adolescent Philippine residents of Schistosoma japonicum endemic areas Determining immunologic and developmental predictors of resistance in naturally exposed humans is a fundamental component of the ongoing effort to develop vaccines against schistosomiasis japonicum. Development of protective human immune responses to other schistosomes appears to occur during puberty in endemic communities. A recent hypothesis states that the hormonal changes of puberty, e.g., increasing dehydroepiandrosterone (DHEA), not cumulative exposure, initiate and promote the development of protective immune responses to schistosome infections Schistosomiasis is causally linked to malnutrition leading to the hypothesis that chronic infection results in attenuate growth for age and possibly delayed pubertal development. Animal models of chronic parasitemia have identified TNF-alpha and IL-6 as mediators of malnutrition and cachexia. Production of this mediator is significantly attenuated by increasing DHEA levels. These interrelationships suggest that a DHEA-modulated cycle of infection, pubertal delay, and malnutrition may be responsible for the marginal nutritional status of schistosome infected adolescents. This study will employ a longitudinal, treatment-reinfection design of naturally exposed humans to determine the immunologic predictors of resistance to reinfection and their interrelationships with puberty. In addition, the relationships among nutritional status, circulating mediators of inflammation and pubertal hormones will be examined. Information provided by these studies will influence all phases of vaccine development for S. japonicum including the identification of appropriate antigens, protective isotype and cytokine responses and the modulating effects of host pubertal and nutritional development on these responses.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048123-02
Application #
6511530
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Rao, Malla R
Project Start
2001-07-01
Project End
2006-05-31
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
2
Fiscal Year
2002
Total Cost
$607,332
Indirect Cost
Name
Brown University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
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Tu, Zhengkun; Bozorgzadeh, Adel; Pierce, Robert H et al. (2008) TLR-dependent cross talk between human Kupffer cells and NK cells. J Exp Med 205:233-44
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