Diarrhea caused by Cryptosporidium parvum (Cp) is a major cause of morbidity and mortality worldwide for which there is no effective treatment. Immunodeficient persons are at particular risk of the more severe complications of Cp infection, including cholangitis and malnutrition. Scid mice are initially resistant to Cp infection through an interferon gamma (IFNy)-dependent mechanism. The goals of this proposal are to: a) identify the source of rapidly produced IFNy, and b) to show that these cells are necessary for the resistance of mice to acute Cp infection. The relative importance of CD 1 and NK T cells in resistance to Cp challenge will be determined.
In specific aim 1, immunohistochemistry and FACS will also be used to localize IFNy-producing cells in wild-type C57Bl/6 mice.
In specific aim 2, RAG -/- mice will be used to determine to role of T cells in this acute resistance to Cp infection. This will be confirmed by comparing the effect of the adoptive transfer of T cells from IFNy /- and wild-type mice into RAG -/- mice.
In specific aim 3, the roles of NK T cells and CDl in resistance to Cp infection, will be defined by challenging CD1d -/- and NK T cell deficient animals with Cp. In-vitro co-culture of Cp-infected IECs and IELs will be used to show that CD1d is necessary for this interaction. Better understanding of innate immunity to Cp infection in mice may lead to novel therapeutic approaches to this disease for which there is no effective therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AI051581-05
Application #
7091608
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Wali, Tonu M
Project Start
2002-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
5
Fiscal Year
2006
Total Cost
$124,470
Indirect Cost
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
Leav, Brett A; Mackay, Melanie; Ward, Honorine D (2003) Cryptosporidium species: new insights and old challenges. Clin Infect Dis 36:903-8