Abstract

Signal transduction pathways triggered in host cells by the mammalian-infective forms of T. cruzi are required for the invasion process. Specifically the second messengers Ca+2 and cAMP are known effectors of T. cruzi induced host cell signaling. The goals of this proposal are to elucidate these signaling pathways by the identification of the specific host protein factors that are involved. Host cell kinases and phosphatases will be identified and their roles in invasion and/or host cell gene expression will be characterized. The events induced by wild-type T. cruzi will be compared to those induced by a mutant strain that is defective in triggering a specific Ca+2 host cell response, required for invasion of mammalian cells. Finally, cDNA micro array hybridization will be used to identify host cell genes that are differentially expressed during T. cruzi infection.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
3R01AI047960-03S1
Application #
6730095
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Program Officer
Rogers, Martin J
Project Start
2003-04-15
Project End
2004-06-30
Budget Start
2003-04-15
Budget End
2003-06-30
Support Year
3
Fiscal Year
2003
Total Cost
$11,148
Indirect Cost

  Institution

Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Chessler, Anne-Danielle C; Caradonna, Kacey L; Da'dara, Akram et al. (2011) Type I interferons increase host susceptibility to Trypanosoma cruzi infection. Infect Immun 79:2112-9
Costales, Jaime A; Daily, Johanna P; Burleigh, Barbara A (2009) Cytokine-dependent and-independent gene expression changes and cell cycle block revealed in Trypanosoma cruzi-infected host cells by comparative mRNA profiling. BMC Genomics 10:252
Chessler, Anne-Danielle C; Unnikrishnan, Meera; Bei, Amy K et al. (2009) Trypanosoma cruzi triggers an early type I IFN response in vivo at the site of intradermal infection. J Immunol 182:2288-96
Chessler, Anne-Danielle C; Ferreira, Ludmila R P; Chang, Tun-Han et al. (2008) A novel IFN regulatory factor 3-dependent pathway activated by trypanosomes triggers IFN-beta in macrophages and fibroblasts. J Immunol 181:7917-24
Petersen, Christine A; Krumholz, Katherine A; Burleigh, Barbara A (2005) Toll-like receptor 2 regulates interleukin-1beta-dependent cardiomyocyte hypertrophy triggered by Trypanosoma cruzi. Infect Immun 73:6974-80
Unnikrishnan, Meera; Burleigh, Barbara A (2004) Inhibition of host connective tissue growth factor expression: a novel Trypanosoma cruzi-mediated response. FASEB J 18:1625-35
Burleigh, B A (2004) Probing Trypanosoma cruzi biology with DNA microarrays. Parasitology 128 Suppl 1:S3-10
Woolsey, Aaron M; Burleigh, Barbara A (2004) Host cell actin polymerization is required for cellular retention of Trypanosoma cruzi and early association with endosomal/lysosomal compartments. Cell Microbiol 6:829-38
Petersen, Christine A; Burleigh, Barbara A (2003) Role for interleukin-1 beta in Trypanosoma cruzi-induced cardiomyocyte hypertrophy. Infect Immun 71:4441-7
Woolsey, Aaron M; Sunwoo, Lisa; Petersen, Christine A et al. (2003) Novel PI 3-kinase-dependent mechanisms of trypanosome invasion and vacuole maturation. J Cell Sci 116:3611-22

Showing the most recent 10 out of 12 publications