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 the trypanosomosis resistance QTL Tir1. Tir1 has the largest effect of those loci so far detected which influence degree of resistance to murine trypanosomosis caused by Trypanosoma congolense infection. We therefore studied the 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 gene on a > 99% C57BL/6 (resistant) background. We also examined the responses 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. Mice 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. This was comparable to 71 days for control wild-type mice, and 61 and 111 days for mice of the susceptible A/J and resistant C57BL/6J strains, respectively. In mice of the deletion line, the C57BL/6 TNF-alpha allele tended to be 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. congolense infection in mice.