Grant: Joint Canada-Israel Health Research Program

We propose to investigate the therapeutic potential of inhibiting a class of proteins named protein tyrosine phosphatases (PTPs) to promote the resolving of infectious diseases such as tuberculosis. Diseases that result from an infection are most often resolved by cells that are implicated into mediating an immune response to clear foreign agents. These cells include macrophages, which are the predominant type of cells that eliminates infectious agents in a process called phagocytosis, which consists of "eating" the foreign particles. There are two specialized subsets of macrophages that exist: the pro-inflammatory and anti-inflammatory macrophages. Of interest to this research proposal are the pro-inflammatory macrophages, also called M1, which are responsible for triggering an immune response against infectious agents to promote their killing. Recent findings from our laboratories suggest that mice in which PTPRO, a member of the PTP family that acts as a receptor, is inhibited have an increased number of macrophages produced in the bone marrow, while another member, PTP1B, leads to a pro-inflammatory response in macrophages. We hypothesize that certain protein tyrosine phosphatases favor the generation of the pro-inflammatory M1 macrophages, thereby regulating the functions of macrophages leading to promoting immune surveillance and killing of intracellular infectious agents. We propose that regulating the expression and activity of these PTPs may improve the function of this subset of macrophages and promote better anti-pathogenic responses. This research program will provide understanding of infectious disease progression and would contribute to the development of new methods of treatment for infectious diseases by regulating specific PTPs.