Exploitation of host cell signaling machinery: activation of macrophage phosphotyrosine phosphatases as a novel mechanism of molecular microbial pathogenesis

Intracellular pathogens, particularly those that target host mononuclear ph agocytes, have evolved strategies to either evade or inhibit cellular mecha nisms of host defense, Mycobacterium tuberculosis and Leishmania donovani e xemplify a diverse group of microorganism that have developed the ability t o invade and replicate within host macrophages, leading to disease expressi on. Recent studies have suggested that the pathogenesis of intracellular in fection may involve interference with host cell signaling, Drawing upon exa mples from in vitro models that focused on M. tuberculosis and L. donovani, we review evidence that activation of host cell phosphotyrosine phosphatas es may contribute to pathogenesis. A leading candidate appears to be the Sr c homology 2 domain containing phosphotyrosine phosphatase SHP-1, the activ ation of which may contribute to the development of infection and disease p rogression.