Legionella pneumophila is a significant human lung pathogen that is responsible for many community- and hospital- acquired cases of pneumonia. An important part of the pathogenesis of Legionella infection is its ability to grow inside of macrophages. Interestingly, different inbred strains of mice exhibit differences in the permissiveness of their macrophages for the intracellular replication of Legionella, and these differences have been attributed to genetic differences in one of the mouse Neuronal Apoptosis Inhibitory Protein (Naip) genes. The goals of this project are to: Establish the identity of the Naip gene and its mutations that are responsible for the differences in Legionella permissiveness, and to study the function of the Naip proteins by identifying critical interacting proteins that participate in its molecular function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049987-05
Application #
7005699
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Korpela, Jukka K
Project Start
2002-02-15
Project End
2007-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
5
Fiscal Year
2006
Total Cost
$293,927
Indirect Cost
Name
Harvard University
Department
Genetics
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
Coers, Jorn; Vance, Russell E; Fontana, Mary F et al. (2007) Restriction of Legionella pneumophila growth in macrophages requires the concerted action of cytokine and Naip5/Ipaf signalling pathways. Cell Microbiol 9:2344-57
Ren, Tao; Zamboni, Dario S; Roy, Craig R et al. (2006) Flagellin-deficient Legionella mutants evade caspase-1- and Naip5-mediated macrophage immunity. PLoS Pathog 2:e18
Zamboni, Dario S; Kobayashi, Koichi S; Kohlsdorf, Tiana et al. (2006) The Birc1e cytosolic pattern-recognition receptor contributes to the detection and control of Legionella pneumophila infection. Nat Immunol 7:318-25
Wright, Edward K; Goodart, Sheryl A; Growney, Joseph D et al. (2003) Naip5 affects host susceptibility to the intracellular pathogen Legionella pneumophila. Curr Biol 13:27-36