Genetic control of responses to Trypanosoma cruzi in mice: Multiple genes influencing parasitemia and survival

Abstract

Inbred strains of mice can be divided into two groups based on the level of parasitemia which develops after injection with 103 trypomastigotes of Trypanosoma cruzi (Peru). Strains which developed parasitemias of greater than 107 trypomastigotes per ml by day 17, including C3H/HeJ, BALB/c, and CBA/N mice, were termed high parasitemia strains. Low parasitemia strains, including C57BL/6J and DBA/2J mice, developed parasitemias of less than 5 x 106 trypomastigotes per ml by day 17 of infection. Congenic mice from C57BL/10J, C57BL/6J, and BALB/c backgrounds which differed at the H-2 region were injected with 103 trypomastigotes to determine the effect of the H-2 locus on response to infection. The H-2 locus had no effect on the level of parasitemia attained during infection. However, one strain, B10.S (H-2(s)), was unusual in that most of the mice survived infection. The results of infection of F1 hybrid progeny with T. cruzi (Peru) suggest that the low parasitemia response is inherited in a dominant manner and that survival may be influenced by several other genes. The response to T. cruzi infection in inbred mice, as measured by parasitemia and survival time, was influenced by several genes. One or more genes, located outside the H-2 region, were involved in regulating the level of parasitemia reached during infection. Another H-2-linked gene(s) was involved in survival of the infection and appeared to be unique to the H-2(s) haplotype.