How are antibodies involved in the protective mechanism of susceptible mice infected with T. cruzi?

Host resistance to Trypanosoma cruzi is dependent on both natural and acquired immune responses. During the acute phase of the infection the presence of IFN-gama, TNF-alpha, IL-12 and GM-CSF has been closely associated with resistance, whereas TGF-beta and IL-10 have been associated with susceptibility. Several investigators have demonstrated that antibodies are responsible for the survival of susceptible animals in the initial phase of infection and for the maintenance of low levels of parasitemia in the chronic phase. However, how this occurs is not yet understood. Our results and other data in the literature support the hypothesis that the protective role of antibodies in the acute phase of infection is dependent mostly on their ability to induce removal of bloodstream trypomastigotes from the circulation in addition to other concomitant cell-mediated events.

Clearance-inducing antibodies are responsible for protection against the acute phase of Trypanosoma cruzi infection in mice

A study was conducted on mice infected with strains Y and CL of Trypanosoma cruzi. The ability of anti-Y and anti-CL sera to induce complement-mediated lysis, immune clearance and protection against the acute phase of the infection was studied using homologous anti-Y or anti-CL serum tested with the Y or CL strain, or heterologous anti-Y serum tested with the CL strain or anti-CL serum tested with the Y strain. Complement-mediated lysis was induced by both homologous and heterologous antisera but protection was afforded only by homologous antisera. Immune clearance was induced by homologous but not by heterologous antisera. Antisera with high clearance ability were able to confer protection whereas antisera with high lytic ability were not. These results show a high correlation between the antibody ability to induce clearance and to confer protection and suggest that clearance rather than lysis is responsible for protection against the acute phase of the infection. The mechanisms of antibody protection against the acute phase of the infection is discussed.

Specificity and role of anti-Trypanosoma cruzi clearance antibodies

Two strains of Trypanosoma Cruzi (Y and CL) were used to study the specificity and role of anti-T. cruzi clearance antibodies. Clearance antibodies were only induced after immunization with living blood-stream trypomastigotes (Btrys) but not with dead parasites. Btrys of either strain were readily cleared from the circulation after passive immunization with anti-Y or anti-CL scrum provided that the homologous strain was used. CL or Y Btrys sensitized in vitro with the homologous or heterologous antiserum and transferred to normal mice were cleared from the circulation only when the homologous antiserum was used. Clearance antibodies were removed from serum by absorption with the homologous but not with the heterologous strain. Clearance antibodies were removed from serum by absorption with living Btrys but not with fixed parasites. These results suggest that: a) the parasite epitopes involved in the clearance are peculiar to each strain, b) the clearance antibodies are specific to these epitopes, and c) a proper conformation of the parasite antigens is required for the induction and effector activity of the clearance antibodies.

Role of platelets and complement in the clearance of epimastigote forms of Trypanosoma cruzy

1. Trypanosoma cruzi epimastigote forms are very rapidly removed from the circulation of normal and C5-deficient mice. Depletion of C3 by cobra venom factor results in a significant delay in parasite clearance. 2. During parasite clearance there is a significant decrease in the number of circulating platelets and parasite clearance is considerably delayed in thrombocytopenic animals. 3. In vitro incubation of epimastigote forms with normal mouse serum leads to the formation of parasite clumps provided that platelets are present. Innactivation of factor B or depletion of C3 prevents this phenomenon. 4. When epimastigotes are incubated with normal mouse serum they absorb one or more factors required for their aggregation with platelets. 5. It is suggested that in mice T. cruzi epimastigote forms are removed from circulation by the alternative pathway of complement activation and that both C3 and platelets are required for parasite clearance

Role of platelets in the in vivo removal of T. cruzi from circulation

The possible role of platelets in the clearance of Trypanosoma cruzi was studied in vivo in A/sn female mice. Platelet depletion achieved by anti-platelet IgG antibodies induced a significant, though not total, reduction in the rate of removal of T. cruzi bloodstream trypomastigotes (BTRYS) from the circulation. Furthermore, during removal of T. cruzi BTRYS from the circulation of normal mice there was a simultaneous decrease in the number of platelets. These results suggest that platelets play a role in the in vivo mechanism of defense against T. cruzi infection

Role of the mononuclear phagocytic system in the immune and nonspecific clearance of Trypanosoma cruzi bloodstream trypomastigotes

The removal of T. cruzi bloodstream trypomastigotes (BTRYS) from the circulation is mediated mostly by the mononuclear phagocytic system (MPS). In the present study we investigated the the nonspecific and the immune clearance of BTRYS in groups of 4 mice whose MPS activity was either enhanced by BCG treatment or depressed by silica treatment. Treatment with BCG resulted in a significant increase in the nonspecific clearance of both carbon particles (100% after 6 min) and BTRYS (60% after 5 min) 28 days after BCG treatment but there was no change in the immune clearance of the parasites. Pretreatment of the animals with silica induced a significant reduction of the colloidal carbon clearance (80% less than control 15 min later) but did not alter the nonspecific or the immune clearance of BTRYS. We conclude that the removal of the opsonized parasites from the circulation is due to a mechanism different from that of the nonspecific clearance