The goal of this grant proposal is to determine the role of eosinophils in the innate and adaptive immune response of mice to the nematode parasite Strongyloides stercoralis. In previous studies we have shown that protective immunity to this parasite is dependent on IL-5 and on eosinophils. This grant proposal will use a variety of methods to describe the mechanism of cosinophil involvement in immunity including: (1) the use of cytokine and eosinophil granule product transgenic (TG) and knockout mice (KO) mice (2) the use of combinatorial genetics with the TG and KO mice and (3) the testing and quantifying of the role of murine eosinophil granule products in the innate and the adaptive immune response. The specific goals of this project are: (1) To determine the role of eosinophils in killing larval S. stercoralis by the innate immune response. In this section we will determine if killing of larval S. stercoralis by the innate immune response is dependent on granule release from the eosinophils in the immediate environment of the larvae and which specific mouse eosinophil granule products are capable of killing larvae in vitro and in vivo. (2) To determine the role of eosinophils in the induction of the adaptive immune response to larval S. stercoralis. Three roles for eosinophils in the induction of the immune response will be evaluated, cytotoxic cells capable of killing and lysing the larvae antigen presenting cells and cytokine producing cells. (3) To determine the role of eosinophils in killing parasites through the adaptive immune response. In this final section we will determine how eosinophils participate in killing larvae in collaboration with IgM and complement. In conclusion, in this proposed study we will determine how eosinophils contribute in the protective immune response to S. stercoralis and in addition we will determine the role of these cells in the transition from the innate to the adaptive immune response to this infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
3R01AI047189-04S1
Application #
6888439
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Wali, Tonu M
Project Start
2000-12-01
Project End
2005-11-30
Budget Start
2004-05-01
Budget End
2004-11-30
Support Year
4
Fiscal Year
2004
Total Cost
$33,586
Indirect Cost
Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
053284659
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Bonne-Année, Sandra; Hess, Jessica A; Abraham, David (2011) Innate and adaptive immunity to the nematode Strongyloides stercoralis in a mouse model. Immunol Res 51:205-14
O'Connell, Amy E; Hess, Jessica A; Santiago, Gilberto A et al. (2011) Major basic protein from eosinophils and myeloperoxidase from neutrophils are required for protective immunity to Strongyloides stercoralis in mice. Infect Immun 79:2770-8
O'Connell, Amy E; Redding, Kevin M; Hess, Jessica A et al. (2011) Soluble extract from the nematode Strongyloides stercoralis induces CXCR2 dependent/IL-17 independent neutrophil recruitment. Microbes Infect 13:536-44
O'Connell, A E; Kerepesi, L A; Vandergrift, G L et al. (2009) IL-4(-/-) mice with lethal Mesocestoides corti infections--reduced Th2 cytokines and alternatively activated macrophages. Parasite Immunol 31:741-9
Stein, Louis H; Redding, Kevin M; Lee, James J et al. (2009) Eosinophils utilize multiple chemokine receptors for chemotaxis to the parasitic nematode Strongyloides stercoralis. J Innate Immun 1:618-30
Padigel, Udaikumar M; Stein, Louis; Redding, Kevin et al. (2007) Signaling through Galphai2 protein is required for recruitment of neutrophils for antibody-mediated elimination of larval Strongyloides stercoralis in mice. J Leukoc Biol 81:1120-6
Padigel, Udaikumar M; Hess, Jessica A; Lee, James J et al. (2007) Eosinophils act as antigen-presenting cells to induce immunity to Strongyloides stercoralis in mice. J Infect Dis 196:1844-51
Kerepesi, Laura A; Hess, Jessica A; Leon, Ofra et al. (2007) Toll-like receptor 4 (TLR4) is required for protective immunity to larval Strongyloides stercoralis in mice. Microbes Infect 9:28-34
Kerepesi, Laura A; Hess, Jessica A; Nolan, Thomas J et al. (2006) Complement component C3 is required for protective innate and adaptive immunity to larval strongyloides stercoralis in mice. J Immunol 176:4315-22
Galioto, Ann Marie; Hess, Jessica A; Nolan, Thomas J et al. (2006) Role of eosinophils and neutrophils in innate and adaptive protective immunity to larval strongyloides stercoralis in mice. Infect Immun 74:5730-8

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