Immunopathogenesis of cerebral toxoplasmosis.

Abstract

Interferon (IFN)-gamma is an absolute requirement for resistance against acute acquired infection with Toxoplasma gondii and development of toxoplasmic encephalitis (TE) during the late stage of infection. Multiple populations of both T and non-T cells are important sources of IFN-gamma in resistance. In the absence of IFN-gamma-producing non-T cells, T cells cannot prevent TE. Interleukin-12, Bcl-3, NF-kappaB(2), and CD40-CD40L ligand interaction are important for up-regulation of IFN-gamma production. T. gondii infects a variety of host cells, and IFN-gamma-mediated immune responses control the parasite in both phagocytic and nonphagocytic cells through at least five different mechanisms, most likely depending on the types of cells responding to IFN-gamma. Such effector functions involve production of NO by iNOS, tryptophan degradation by the enzyme IDO (indolamine 2,3-dioxygenase), unidentified mechanism(s) mediated by 47- to 48-kDa proteins encoded by an IFN-gamma responsive gene family, limiting the availability of intracellular iron to the parasite, and production of reactive oxygen intermediates.