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Mechanisms of self-cure from Trypanosoma congolense infection in mice
Abstract:
The mechanism(s) of resistance to African trypanosomiasis caused by Trypanosoma congolense was investigated by using the Dinderesso/80/CRTA/3 isolate to which C57B1/6 are resistant (low parasitemia and self-cure) and BALB/c sensitive (high parasitemia and death). The resistance of C57B1/6 is similar to that found in some natural hosts of African trypanosomes such as certain indigenous West African cattle and wild Bovidae. The antibody response to epitopes exposed on the variant surface glycoprotein of a clone obtained from the Dinderesso/80/CRTA/3 isolate was measured by a complement-mediated lysis assay in C57B1/6 and BALB/c. After infections with 10(4), 10(5), or 10(7) motile organisms, antibody appeared in C57B1/6 4 to 8 days earlier than in BALB/c. Peak antibody titers were similar in both strains but were reached about 4 days earlier in C57B1/6. In this strain, antibody appeared during and controlled the first wave of parasitemia, whereas in BALB/c, parasitemia reached a plateau above 10(8) organisms per ml before antibody could be detected, and at this time the animals were dying. At peak antibody response, the proportion of immunoglobulin (Ig) M and IgG antibody was the same in both strains. The antibody response had the same kinetics in C57B1/6 and BALB/c after injection of 10(4), 10(5), and 10(7) lethally irradiated but intact parasites, but the peak titers were 10(3) to 10(4) times lower than after live challenge. The response to nonirradiated trypanosomes appeared to be T cell independent, because the antibody titers were the same in congenitally athymic nu/nu and normal C57B1/6, and no evidence for the induction of T cell activity could be demonstrated in the infected nude mice. A role for trypanolytic serum factors in resistance could not be demonstrated. The extent of immunosuppression after infection with nonirradiated organisms was compared in the two strains by measuring the in vitro response of their splenic lymphocytes to concanavalin A, pokeweed mitogen, and allogeneic cells and their ability to mount an in vivo response to an unrelated trypanosome challenge. Both strains were partially immunosuppressed during rising parasitemia, but as C57B1/6 controlled parasitemia, immunosuppression was gradually reversed, whereas in BALB/c it became worse. Several explanations might account for the resistance of C57B1/6 to the Dinderesso/80/CRTA/3 isolate of T. congolense. It appears that an early immune response is a decisive factor in this resistance.
Insights
C57B1/6 mice exhibit resistance to Trypanosoma congolense by mounting an early antibody response that controls parasitemia. BALB/c mice, however, show high parasitemia and succumb to infection, indicating a critical role for early immunity in African trypanosomiasis resistance.
Area of Science:
- Immunology
- Parasitology
- Veterinary Medicine
Background:
- African trypanosomiasis, caused by Trypanosoma congolense, presents varying resistance levels in different hosts.
- C57B1/6 mice demonstrate resistance (low parasitemia, self-cure), while BALB/c mice are sensitive (high parasitemia, death).
- This differential susceptibility mirrors resistance observed in natural hosts like West African cattle.
Purpose of the Study:
- To investigate the immunological mechanisms underlying resistance to Trypanosoma congolense in C57B1/6 mice compared to susceptible BALB/c mice.
- To elucidate the role of antibody response kinetics and T-cell independence in trypanosome resistance.
Main Methods:
- Comparative analysis of antibody response (complement-mediated lysis assay) to variant surface glycoprotein in infected C57B1/6 and BALB/c mice.
- Assessment of T-cell independence by comparing antibody titers in athymic (nu/nu) and normal C57B1/6 mice.
- Evaluation of immunosuppression extent via in vitro lymphocyte proliferation and in vivo challenge responses.
Main Results:
- C57B1/6 mice developed antibodies 4-8 days earlier than BALB/c mice, controlling the initial parasitemia wave.
- Peak antibody titers were similar, but reached sooner in resistant C57B1/6 mice.
- The antibody response to non-irradiated trypanosomes was T-cell independent, and immunosuppression was reversible in resistant mice but worsened in sensitive mice.
Conclusions:
- An early and effective antibody response is a decisive factor in C57B1/6 resistance to Trypanosoma congolense.
- The resistance mechanism appears to be T-cell independent, highlighting the crucial role of humoral immunity.
- Differential control of parasitemia and immunosuppression reversal contribute to host survival in African trypanosomiasis.