Improving microphage innate immunity by modulating protein tyrosine phosphatases: The complete mouse and human PTPomes

Diseases that result from an infection are most often resolved by cells that use an immune response to clear foreign agents. These cells include macrophages, which are the predominant type of cell that eliminates infectious agents in a process called phagocytosis, or “eating” the foreign particles. There are two specialized subsets of macrophages: pro-inflammatory and anti-inflammatory macrophages. This research focuses on the pro-inflammatory macrophages, also called M1, which are responsible for triggering an immune response against infectious agents to promote their killing.

This project investigates the therapeutic potential of inhibiting a class of proteins named protein tyrosine phosphatases (PTPs) to treat infectious diseases. Recent findings suggest that mice in which PTP-RO is inhibited have an increased number of macrophages in the bone marrow, while PTP-1B leads to a pro-inflammatory response in macrophages. The authors hypothesize that certain PTPs favour the generation of the pro-inflammatory M1 macrophages, thereby regulating the functions leading to promoting immune surveillance and killing of infectious agents. The project proposes that regulating the expression and activity of these PTPs may improve the function of these macrophages and promote better anti-pathogenic responses.

The research will improve understanding of infectious disease progression and contribute to the development of new methods of treatment for infectious diseases by regulating specific PTPs. The project is led in Canada by McGill University, with the collaboration of the Weizmann Institute (Israel) and the University of Hyderabad (India).

This project was selected and approved for funding through the second research competition of the Joint Canada-Israel Health Research Program, a partnership between Canada’s International Development Research Centre, the Canadian Institutes for Health Research, the Israel Science Foundation, and the Azrieli Foundation. This 7-year, $35M Canadian-Israeli effort draws on the unique scientific strengths of both countries and facilitates networking opportunities with peers from Africa, Asia, and Latin America. All projects include a plan for integrating researchers from low- and middle-income countries that will establish long-term scientific relationships.

Project ID

108406

Project status

Active

Duration

36 months

IDRC Officer

Fabiano Santos

Total funding

CA$ 669,831

Country(s)

Canada, Israel

Project Leader

Michel L. Tremblay

Institution

The Royal Institution for the Advancement of Learning/McGill University

Institution Country

Canada

Institution Website

http://www.mcgill.ca