PubMed:10631575 JSONTXT 2 Projects

Genes, cells and cytokines in resistance against development of toxoplasmic encephalitis. Toxplasma gondii is an intracellular protozoan parasite which invades various organs including the central nervous system. Immunity is crucial for preventing development of toxoplasmic encephalitis (TE) following infection. IFN-gamma-mediated immune response plays a central role in the resistance. The activation of microglia and astrocytes by IFN-gamma or a combination of this cytokine with TNF-alpha appears to be an important effector mechanism in the host immunity. GM-CSF, IL-1 beta and IL-6 may participate in this activation. iNOS is a molecule which mediates the protective activity of the activated murine microglia and human astrocytes; however, another unknown mechanism(s) not mediated by iNOS is involved in the activity of activated murine astrocytes and human microglia. IL-6 plays a protective role, at least in part, by up-regulating IFN-gamma production during the chronic stage of infection in mice. IL-6 also plays a role in regulating the infiltration of T cell subsets into the brain. IL-4 appears to play a protective role, but its role may differ depending on the strains of mice. In contrast to these protective cytokines, IL-10 may play a pathogenic role by down-regulating IFN-gamma production. The resistance against development of TE is under genetic control in both mice and humans. The Ld gene within the D region of the H-2 complex confers resistance in mice. In AIDS patients, HLA-DQ3 appears to be a genetic marker of susceptibility, and HLA-DQ1 appears to be a resistance marker. Strains (genetic variation) of T. gondii is another factor which affects the susceptibility of the host to the development of TE. The genotypes of the parasite may be important for determining the susceptibility. It is possible that the genes of the host and genetic variation of T. gondii affect immune response of the host to the parasite, and thereby contribute to determining the resistance against the development of TE.