Phagocytosis is critical for the elimination of invading pathogens, foreign particles, and dead cell bodies. Impairment of this process results in the development of disease, including infectious diseases. Surprisingly, despite the importance of this pathway, limited information is available regarding the mechanism(s) controlling phagosome maturation. In particular, the identity of the SNARE complexes controlling the fusion of the endocytic compartments with the phagosomes is incomplete. We have recently identified that the SNARE protein SNAP29 plays an early role in the killing of Escherichia coli by macrophages. Based on this discovery, we propose to address the hypothesis that SNAP29 forms fusogenic complex(es) with early endocytic SNAREs to control the early step of phagosome maturation. Using a unique multi-disciplinary approach, we will identify and characterize SNAP29-containing complexes involved in E. coli phagocytosis. In parallel, we will identify which early endocytic SNAREs play a role in E. coli phagocytosis, regardless of being involved with SNAP29. The information gathered during the course of this project is necessary to 1) understand how professional phagocytic cells such as macrophages eliminate bacteria, 2) identify molecular targets that intracellular bacteria such as Salmonella typhimurium or Mycobacterium tuberculosis may compromise to escape killing, and 3) guide the development of new strategies to fight infectious diseases.

Public Health Relevance

Phagocytosis is the process by which immune cells such as macrophages engulf and kill invading pathogens. We propose to dissect the molecular machinery involved in phagosome maturation and identify key regulators of this process. The data generated during the course of this study will guide the design of new strategies to fight infectious diseases.

Agency
National Institute of Health (NIH)
Type
Small Research Grants (R03)
Project #
1R03AI111091-01
Application #
8683383
Study Section
Innate Immunity and Inflammation (III)
Program Officer
Palker, Thomas J
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19107