Susceptibility of tumour necrosis factor-alpha genetically deficient mice to Trypanosoma congolense infection

The TNF-alpha gene on mouse chromosome MMU17 is among the candidates for th e trypanosomosis resistance QTL Tir1. Tir1 has the largest effect of those loci so far detected which influence degree of resistance to murine trypano somosis caused by Trypanosoma congolense infection. We therefore studied th e survival to 180 days after challenge with T. congolense of mice that were homozygous and hemizygous with respect to a disruption of the TNF-alpha ge ne on a > 99% C57BL/6 (resistant) background. We also examined the response s of TNF-alpha hemizygous mice produced by crossing the deletion line with mice of the C57BL/6J strain, and with mice of the susceptible A/J strain. M ice lacking a functional TNF-alpha gene were shown to be highly susceptible to challenge with T. congolense with a median survival time of 37 days. Th is was comparable to 71 days for control wild-type mice, and 61 and 111 day s for mice of the susceptible A/J and resistant C57BL/6J strains, respectiv ely. In mice of the deletion line, the C57BL/6 TNF-alpha allele tended to b e dominant to the TNF knockout in terms of resistance. We conclude that TNF -alpha plays an important role in resistance to the effects of T. congolens e infection in mice.