Regulation of the growth and differentiation of Trypanosoma (Trypanozoon) brucei brucei in resistant (C57B1/6) and susceptible (C3H/He) mice

Abstract

While Trypanosoma brucei brucei GUTat 3 were equally infective for C3H/He and for C57Bl/6 mice at doses ranging from 5 to 5 x 10(3) organisms and had similar prepatent periods in both strains of mice, infected C57Bl/6 mice displayed lower parasitaemia, shorter times to parasite wave remission and survived for a longer time than infected C3H/He mice. Parasite growth and differentiation rates and host immune responses were similar for the first 5 days in both strains of mice after infection with 10(3) T.b.brucei GUTat 3 but, thereafter, parasite differentiation proceeded more rapidly and specific antibodies reached higher titres in C57Bl/6 than in C3H/He mice. In contrast, parasite growth and differentiation rates were similar in irradiated mice of both strains. Furthermore, following inoculation of intact mice with irradiated T.b.brucei GUTat 3, C3H/He mice actually mounted higher titred antibody responses than C57Bl/6 mice showing that they were not intrinsically defective in their capacity to respond to GUTat 3 antigens. Parasite differentiation occurred at the same rate in irradiated (650r) C57Bl/6 mice and in irradiated C57Bl/6 mice reconstituted with syngeneic spleen cells although T.b.brucei GUTat 3 specific antibody was detected in the latter mice prior to peak parasitaemia. Furthermore, it was shown directly in C57Bl/6 mice that there was no selective destruction of slender form T.b.brucei GUTat 3 parasites during the phase of accumulation of stumpy form parasites. These studies indicate that the more rapid differentiation of T.b.brucei GUTat 3 parasites in infected C57Bl/6 mice as compared to infected C3H/He mice was unlikely to be directly related to the more efficient antibody response in the infected C57Bl/6 mice. The observations suggest that there might be an association between host mechanisms which regulate differentiation of T.b.brucei parasites and those which regulate antibody responses.

Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate

“…Thus, if antibody responses were responsible for these observations the functional activity of the antibody response would have had to increase by the same proportion with each 10-fold increase in inoculum size. Such a linear relationship between the antibody response and the quantity of trypanosome antigen is inconsistent with experimental findings (8). Furthermore, by extrapolation from experiments carried out with cattle, it would appear that the smallest inoculum sizes used in our experiment would be insufficient to elicit an anti-variant-specific surface glycoprotein response (32).…”

“…The maximum concentration that a trypanosome population attains in rodents is regulated by both host factors (7,8) and host-independent mechanisms associated with the parasite population (9). The results described here have demonstrated that diminazene susceptibility is dependent upon the concentration of a trypanosome population in vivo.…”

“…Following treatment, blood samples were obtained from mice in each of groups A, B, and C after 5, 10, 15, 30, 40, and 45 min and 1, 1.5, 2, 3, 4,6,8,10,12,14,16,18,21,24, and 48 h. Since ion pair extraction of diminazene from blood (2) requires a volume of 1 ml, samples from two treated mice were pooled in a 3-ml potassium-EDTA-containing Vacutainer (Becton Dickinson) tube for each time. Furthermore, at each sampling time, 10 mice were used to obtain five replicate samples.…”

“…Growth and differentiation of trypanosomes appear to be regulated by both host (7,8,38) and parasite (4,9,37,39) factors. There is also evidence that cyclic AMP (cAMP) is directly involved in such regulation, since high levels of parasitemia have been shown to be associated with an elevation in intracellular levels of cAMP and prolongation of the doubling time in Trypanosoma brucei brucei (29).…”

Cytokines and antibody responses during Trypanosoma congolense infections in two inbred mouse strains that differ in resistance

“…Resistant strains of mice have earlier and higher serum anti-VSG antibody response than susceptible strains (Black et al 1983, Whitelaw et al 1983, Mitchell & Pearson 1986). Because it has been shown that nude mice infected with T. brucei rhodesiense were capable of controlling their first wave of parasitaemia (Campbell, Esser & Philips 1978), one could argue that an IgM anti-VSG antibody response is sufficient to control variant specific parasitemia (Mansfield 1990).…”