Amastigotes of Trypanosoma cruzi escape destruction by the terminal complement components.

Abstract

In the absence of antibody, the alternative pathway of the complement system can function as a first barrier in preventing infection. However, certain microorganisms have developed mechanisms to escape attack and survive in the host's bloodstream (1). Trypanosoma cruzi, the causative agent of Chagas' disease, is a protozoan parasite that cycles between invertebrate insect vectors and mammalian hosts. During its development in the insect, T. cruzi assumes various forms and the infectivity of the parasite for the mammalian host is associated with the aquisition of resistance to lysis by complement (2-5). The epimastigote is the noninfective multiplicative form found in the gut of the insect . Epimastigotes transform into metacyclic trypomastigotes, which can invade cells of the mammalian host. While both epimastigotes and metacyclics activate the complement cascade, only epimastigotes are lysed. Metacyclics are not lysed because they have developed mechanism(s) to prevent the assembly of C3 convertase, a key amplifying enyzme of the complement system (6-9).When trypomastigotes enter the host cells, they transform into amastigotes; the amastigotes then mulitply, transform again into trypomastigotes, and are released into the bloodstream to continue the cycle. Contrary to the conventional view that amastigotes are exclusively the intracellular multiplicative stage of the parasite, recent studies demonstrate that amastigotes can be found in circulation during the acute stages ofthe infection and can enter and develop in cells (10). In vitro infection of monocytes by amastigotes occurs in the presence of fresh human serum, indicating that they also avoid destruction by complement . These studies, however, did not discriminate between lack ofcomplement activation and protection from attack .Here, we address this question and show that amastigotes are extremely efficient activators of the cascade and that they bind terminal components . Functional channels, however, are not formed and the parasites are not destroyed. Volume 169 March 1989 881-891 Materials and MethodsParasites . Strain Y of T, cruzi was maintained in monolayers of LLC-MK2 cells in DMEM containing 5% FCS at 37 0C in a 5°Jo C02 atmosphere. Amastigotes were obtained as follows. Trypomastigotes were collected from a 5-d culture of infected cells within 24 h after changing the medium . As determined by light microscopy, most trypomastigotes transformed into

Carbohydrate immunity in American trypanosomiasis

“…Epimastigotes but not trypomastigotes are lysed by mammalian sera in the absence of specific antibodies. Amastigotes are extremely efficient activators of the complement cascade but functional channels are not formed and the parasites are not destroyed [36]. Lysis of trypomastigotes can only be obtained by activation of the alternative pathway of complement after modification of the cell surface, e.g., by sialidase or trypsin treatment [42].…”

A role for extracellular amastigotes in the immunopathology of Chagas disease

“…Once released to extracellular spaces, the trypomastigotes tend to move away from the primary foci of infection, while the non-motile extracellular amastigotes [which resist C' mediated lysis (Iida et al 1989)] tend to accumulate in the proximity of the primary site of infection (Fig. 2) .…”

Versatile Roles of CspA Orthologs in Complement Inactivation of Serum-Resistant Lyme Disease Spirochetes

“…Binding to the TCC family of homologous proteins (57) has been used as an efficient strategy for protecting invading microorganisms against complement attack, including the parasites Trypanosoma cruzi, Entamoeba histolytica, Schistosoma mansoni, and Trichinella spiralis, but only fragmentary information is available regarding the underlying molecular mechanisms (58)(59)(60)(61)(62). Previous studies illustrate how paramyosin of Schistosoma mansoni and Trichinella spiralis interacts specifically with C8 and C9, leading to an efficient inhibition of TCC assembly (62,63).…”