oa Playing with Fire: Manipulation of Macrophage Proinflammatory Signal Transduction by the Intracellular Protozoan Toxoplasma gondii

The protozoan Toxoplasma gondii is an enormously successful parasite that asymptomatically infects 10-50 percent of the human population worldwide. During immunodeficiency, Toxoplasma emerges as a virulent pathogen causing lethal disease if untreated. The normally innocuous nature of infection is dependent upon the parasite's ability to trigger protective immunity enabling host survival, at the same time avoiding an excessively strong immune response that could cause excessive host pathology. Recent data from our laboratory and others are revealing this key principle in action within the innate immune system. Infection triggers early activation of mitogen-activated protein kinase (MAPK), nuclear factor (NF)κB and signal transducer and activator of transcription (STAT) pathways. Nevertheless, Toxoplasma suppresses other components of proinflammatory signaling, and this is likely to down-modulate effector functions of both macrophages and dendritic cells. The ability of T. gondii to simultaneously activate and suppress signal transduction in infected cells is a likely consequence of the parasite's need to manipulate cellular immunity to achieve a stable interaction at the host-parasite interface.