and specific aims): Tuberculosis is responsible for more human deaths worldwide each year than any other single infectious disease. Current understanding of the pathogenesis of tuberculosis suggests that innate host defenses determine whether mycobacterial infection results in active disease or whether the infection is successfully contained. Host responses designed to limit mycobacterial growth include the activation of leukocytes and the formulation of granulomas. Effective granuloma formation is critical for the control of tuberculosis, and begins with the migration of peripheral leukocytes to the lung. While the production of chemoattractant cytokines by infected alveolar macrophages is likely to stimulate leukocyte recruitment, the effect of specific mycobacterial products on this response has yet to be determined. This application hypothesizes that the release of the mycobacterial cell wall glycophospholipid lipoarabinomannan (LAM) from infected alveolar macrophages serves to recruit peripheral T cells to the site of infection, and subsequently suppress the activation of these migrating T cells.
The specific aims are: 1) to characterize the function and phenotype of leukocytes which migrate to LAM; 2) to define a mechanistic basis for the chemotactic response of leukocytes to LAM; and 3) to determine the molecular basis for suppression of leukocyte activation by LAM.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL055681-02
Application #
2735301
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1997-07-20
Project End
2002-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Boston University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118