Resistance of Trypanosoma cruzi to killing by macrophages

CHAGAS' disease is a chronic debilitating illness, widespread in Latin America, caused by infection with the haemoflagellate, Trypanosoma cruzi. Antibodies to the organism, commonly present in both the acute and chronic forms of the disease, have generally been ineffective in protecting animals against infection^1,2. There is ample pathological documentation of the involvement of macrophages in Chagas' disease^3-5 but unfortunately little is known about their function, or of the role of cell-mediated immunity in general. It has, however, been shown that passive transfer of immune spleen cells can protect mice against T. cruzi infection¹. Because macrophages serve as effector cells in protecting against intracellular parasites, we have studied the interaction of T. cruzi and macrophages in vitro. Preliminary experiments showed that at low parasite-macrophage ratios (for example 1) most cultures of normal uninduced mouse peritoneal macrophages could eliminate the infection and survive; in contrast, with higher ratios (for example 10), they were destroyed⁶. Mackaness⁷ has shown that macrophages can be 'activated' after immunisation and challenge with specific antigen to become non-specifically resistant to other infecting bacteria. We report here that nonspecifically 'activated' macrophages have heightened resistance to intracellular growth of T. cruzi, and suggest that its absence in normal macrophages is related to the ability of the parasite to escape from the phagolysosomes into the cytoplasm.