Antibody-Independent, Natural Resistance of Birds to Trypanosoma cruzi Infection

Abstract

Complement (C) activity present in normal human serum has been reported to lyse circulating forms of Trypanosoma cruzi following activation by specific host antibodies bound to the surface of the parasites. In view of this observation, we examined the possibility that a similar phenomenon may cause lysis of T. cruzi by avian complement, a mechanism postulated to be responsible for the natural resistance of birds to T. cruzi infection and previously described as being antibody independent. Trypomastigote forms of T. cruzi grown either in lethally irradiated mice or in cell cultures were lysed readily by the sera of agammaglobulinemic chickens. Lytic activity and titers of normal and agammaglobulinemic sera were comparable. The lytic reaction was inhibited by heat inactivation of the sera, or by addition of EDTA or cobra venom factor to the assay mixtures. Lysis of T. cruzi was observed when calcium, but no magnesium ions, were chelated with EGTA. Furthermore, a significant loss of lytic activity was observed when sera from C-depleted chickens were tested. Normal and agammaglobulinemic chickens cleared intravenously injected parasites (from either lethally irradiated mice or cell cultures) from their circulation in 7 min or less whereas C-depleted animals required 1,740 min or longer. Routine examination of the parasites from these two sources by immunofluorescence confirmed the absence of immunoglobulins on their surface. These results emphasize the lack of requirement of antibodies for, and the important role of complement in both the natural resistance that birds exhibit against T. cruzi infection and the lytic activity displayed by avain serum on virulent forms of T. cruzi.

Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

“…However, a clear demonstration of the mechanism of and the part that autoimmunity plays in the development of Chagas' heart disease is essential for the effective delivery of treatment. To demonstrate the important role played independently by autoimmunity in the pathogenesis of Chagas' heart disease, coexisting tissue inflammation with active infection needs to be eliminated (40,203,408,434). An approach to answering this question requires the abrogation of the parasite infection.…”

“…The refractoriness of chickens to T. cruzi is dependent on innate immune factors (281,293 [see comments regarding this retracted article at first citation]) and does not require a natural antibody; bursectomized chicks are refractory to T. cruzi infections (291). The lytic effect of the chicken complement system alternate pathway upon infection by T. cruzi trypomastigotes cannot be totally ruled out (203,204). The refractoriness of chicks is present at hatching (293 [see comments regarding this retracted article at first citation], 402), but the infection can be installed by the inoculation of infective T. cruzi trypomastigotes into the air chamber of fertile chicken eggs; dividing parasite amastigotes can be seen in embryo cells until the eighth day of growth (293 [see comments regarding this retracted article at first citation], 407).…”

Trypanosoma cruzi and Chagas' Disease in the United States

“…To date, over 100 mammalian species have been reported as natural hosts for T. cruzi, and all mammals are considered to be susceptible to infection. Birds are refractory to infection due to complement-mediated lysis and macrophage-induced killing of the parasites (146,188). Although T. cruzi has a wide host range, the epidemiologically important reservoirs vary by geographic region due to the biology and ecology of the mammals and vectors and how these interactions translate to risk of human exposure.…”

Ultrastructural damage of Trypanosoma cruzi epimastigotes exposed to decomplemented immune sera

“…Excepting the destruction of T. cruzi trypomastigotes by avian serum, which is an antibody-independent process, lysis has been reported to be the result of complement activation by speci®c antibodies (Kierszenbaum et al 1981).…”