Alterations of the microcirculatory network during the clearance of epimastigote forms of Trypanosoma cruzi: an intravital microscopic study.

The distribution of epimastigote forms of Trypanosoma cruzi in the microcirculatory network and the vessel alterations were observed using an intravital microscopy technique. Immediately after intravenous inoculation of 2 x 10(6) epimastigote suspension into normal mice, parasites were seen as circulating clumps, and their retention at some sites of the endothelium of venules and capillaries was observed. Injection of 2 x 10(7) and 2 x 10(8) parasite suspensions induced, respectively, intermittent or total stasis of venules and capillaries, probably via obstruction by clumping.

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-gamma, TNF-alpha, IL-12 and GM-CSF has been closely associated with resistance, whereas TGF-ss 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.

Changes of anti-Trypanosoma cruzi antibodies after gamma-irradiation of mice in the chronic phase of the infection.

The effect of sublethal whole body irradiation (800 rads) on the level and biological activities of antibodies in mice chronically infected with the CL strain of Trypanosoma cruzi was studied. Irradiated mice died, although a high parasitemia did not always preceded death. Before and after irradiation, a constant level of antibodies was detected by enzyme-linked immunosorbent assay and complement mediated lysis, but after irradiation the level of clearance antibodies was decreased.

One fate of bloodstream trypomastigote forms of Trypanosoma cruzi after immune clearance: an ultrastructural study.

The fate of bloodstream forms of Trypanosoma cruzi in tissues of mice was studied after immune elimination from circulation. Observations using transmission electron microscopy showed platelet thrombi occluding small vessels in the lung, liver, and spleen, and phagocytosed parasites in different stages of destruction within macrophages, neutrophils, and eosinophils. It is suggested that no particular cell population is a potential effector, but that different cells act in concert to destroy the parasites.

Biological activity of chronic phase antibodies eluted from sensitized Trypanosoma cruzi trypomastigotes.

Chronic infection with Trypanosoma cruzi induces high levels of antibodies that have lytic and clearance activities on bloodstream trypomastigote forms. These two activities were tested with antibodies eluted from parasites sensitized with serum obtained from mice in the chronic phase of infection. Parasites submitted to treatment for antibody elution were also tested.

One fate of epimastigote forms of Trypanosoma cruzi injected in mice. An ultrastructural study.

Recently, we suggested that epimastigote forms of Trypanosoma cruzi are cleared from circulation of mice by a mechanism independent of lysis and that platelets play an important role in this process. These observations prompted us to look at the fate of epimastigotes in the lung, liver, and spleen of mice injected intravenously with these parasite forms. Using transmission electron microscopy, we observed clumps of epimastigotes and platelets in direct contact with phagocytes in the lumen of capillaries.

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.

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.

Role of platelets and complement in the clearance of epimastigote forms of Trypanosoma cruzi.

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.

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.

In-vitro lysis of sensitized Trypanosoma cruzi by platelets: role of C3b receptors.

Incubation of Trypanosoma cruzi bloodstream trypomastigotes (Btrys) with C5-deficient blood in the presence of anti-T. cruzi immune mouse serum (IMS) or its IgG fraction resulted in an immediate formation of small clumps in which one could easily see platelets adhered to the parasites. After 4 h of incubation most of the clumps had disappeared and the number of the parasites was considerably reduced.

The effect of C3 depletion on the clearance of Trypanosoma cruzi induced by IgG antibodies.

Passive transfer of homologous immune serum or IgG anti-Trypanosoma cruzi antibodies to normal mice containing circulating T. cruzi bloodstream trypomastigotes (Btrys) induces a very fast clearance of the parasites. Previous work from this laboratory has shown that F(ab')2 fragments obtained from IgG anti-T.

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

1. The removal of T. cruzi bloodstream trypomastigotes (BTRYS) from the circulation is mediated mostly by the mononuclear phagocytic system (MPS).

Role of the antibody Fc in the immune clearance of Trypanosoma cruzi.

Passive transfer of immune serum obtained from mice chronically infected with Trypanosoma cruzi to mice containing circulating bloodstream trypomastigotes induces a very fast clearance of the parasites. Comparison of trypomastigotes clearance in normocomplementemic and C5-deficient mice showed no difference. IgG fraction obtained from immune serum was very efficient at inducing complement-mediated lysis and immune clearance of bloodstream trypomastigotes, whereas its Fc-missing F (ab') 2 fragments, although able to induce lysis, were unable to induce clearance.