Polymorphisms in the tumor necrosis factor α (TNF-α) gene correlate with murine resistance to development of toxoplasmic encephalitis and with levels of TNF-α mRNA in infected brain tissue

Murine resistance to development of toxoplasmic encephalitis (TE) has recently been mapped to the D region of the major histocompatibility complex (H-2). Since the gene for tumor necrosis factor α (TNF-α) is located 5' of the D region and TNF-α has been implicated as playing a role in neurological diseases, we were interested in determining the relationship of TNF-α production to TE resistance. We have demonstrated that resistance to TE in inbred mice can be correlated with specific restriction fragment length polymorphisms and microsatelite variants in the TNF-α gene. Mice that are susceptible to TE express elevated levels of TNF-α mRNA in brain tissue 6 wk after infection with the ME49 strain of Toxoplasma gondii. Resistant mice and all mice that are uninfected show no detectable TNF-α mRNA expression in brain tissue. Differences in the TNF-α gene between susceptible and resistant mice have been localized to the first intron, the promoter, and the 3' end of the TNF-α gene. These data implicate differences in regulation of TNF-α production in brain tissue as contributing to differences in susceptibility to development of TE.