We recently showed that culture-derived metacyclic trypomastigotes (CMT), but not epimastigotes (Epi), of the Miranda 88 strain of Trypanosoma cruzi evade lysis by the human alternative complement pathway because of inefficient binding of factor B to complement component C3b on the parasite surface. These results suggested that CMT and tissue-culture-derived trypomastigotes (TCT), which also Trypanosoma cruzi, the causative agent of Chagas disease, is a hemoflagellate protozoan that cycles between blood-feeding reduviid insects and various vertebrate hosts including humans. The epimastigote (Epi), which is the major insect stage of the parasite, is highly sensitive to lysis in normal human serum by the alternative complement pathway (ACP). In contrast, the infective metacyclic trypomastigote (which develops in the vector), the vertebrate-blood-form trypomastigote, and the respective culture-derived representatives of these two stages, the CMT (culture-generated metacyclic trypomastigote) and TCT (tissue-culture-derived trypomastigote), are highly resistant to ACP-mediated lysis.We have been studying the developmentally regulated mechanisms responsible for evasion of the ACP by the infective and vertebrate trypomastigote stages of the T. cruzi life cycle. Our studies have shown that upon incubation in human serum, complement-resistant CMT or TCT bind 5-8 times less complement component C3 or C9 than complement-sensitive Epi (1, 2). Furthermore, whereas C3 bound to Epi is mainly in the hemolytically active C3b form, CMT and TCT bear predominantly the hemolytically inactive iC3b fragment. In CMT, this difference appears to be due to inefficient binding of factor B to C3b on the surface of the parasite, such that binding of factor H to C3b is favored instead, resulting in subsequent factor I-mediated cleavage of C3b to iC3b. As a possible explanation of these parasite stage-dependent regulatory events, we now report that both CMT and TCT produce factors that interfere with B binding to C3b, thus diminishing the formation of C3 convertase. We also show that CMT and TCT shed substances into culture medium that accelerate the intrinsic decay of the alternativeand classical-pathway C3 convertases (C3bBb and C4b2a).

Internalization and infectivity of Trypanosoma cruzi trypomastigotes by macrophages is enhanced by prior treatment of parasites with normal human serum. Heating serum or removing Clq from serum abrogates the enhancement, but augmentation of attachment and infectivity is restored by addition of purified Clq to either serum source. Although both noninfective epimastigotes (Epi) Although trypomastigotes produce an inhibitor of the complement cascade which limits C3 deposition during incubation in normal human serum, Clq binds to the parasite and enhances entry of trypomastigotes into target cells.

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Although mice infected with Trypanosoma cruzi develop a wide variety of electrocardiographic (ECG) alterations, the typical isolated right bundle branch block or its association with the left anterior hemiblock patterns are not found in this model. This has been explained as related to topographic differences in the anatomy of the murine conducting system. However, there is no conclusive evidence that the murine conducting system differs from the human system. In this study, the anatomy of the murine conducting system is described, as well as its involvement in the chronic stages of experimental infection. 24 three-month-old C3H mice were infected with 50 bloodstream forms of T. cruzi, Tulahuén strain. Animals were killed after 3, 8 and 12 months. Whole frontal sections of the heart, including the conducting system, were serially studied. The sinoatrial node was located in the right atrial appendage, or in the junction between the superior vena cava and the right atrium, or "riding" on the interatrial septum. The atrioventricular (A-V) node and the His bundle showed a similar anatomic course to that in man. Therefore, there was no important anatomical difference that might have explained the lack of the ECG patterns observed in human chagasic myocardiopathy. The inflammatory involvement and the lesions of the conducting system were diverse and rarely severe. No significant difference was observed in animals killed at different times. The lesions in the working myocardium were similar to those observed in humans (chronic inflammatory infiltrates). Nevertheless, the topography of lesions was different: there was a selective involvement in the neighbourhood of the A-V groove.(ABSTRACT TRUNCATED AT 250 WORDS)

Peripheral blood mononuclear cells (PBMC) and polymorphonuclear leukocytes (PMNL) of patients with Argentine hemorrhagic fever (AHF) were tested as effectors (E) of antibody-dependent cell cytotoxicity (ADCC). 51Cr labeled chicken red blood cells (CRBC) coated with anti-CRBC or normal rabbit serum were used as targets (T). Three ADCC assays were performed with both effectors from patients: on admission (I), 4 days after the transfusion of immune plasma (II), and 30 days after the clinical onset (III). The ADCC values obtained displayed high variation between individuals. From the linear portions in the curves representing specific 51Cr release vs. E:T ratio plots, extrapolations were made to determine lytic units (LU), defined here as effector concentrations required to lyse 50% of the targets. The results were expressed as LU in 10(6) effector cells. The killing activity ranges of patients' PMNL (I = 1.04 +/- 0.34; II = 2.22 +/- 0.66; and III = 2.08 +/- 1.18) were not significantly different from that of 21 normal controls (1.19 +/- 0.36), except for range II (P less than 0.01). ADCC activity ranges of patients' PBMC (I = 3.40 +/- 1.06; II = 3.16 +/- 1.60; and III = 1.93 +/- 0.42) were not significantly different from that determined in 12 healthy subjects (1.86 +/- 0.40). These results demonstrate that patients' PBMC and PMNL can perform ADCC with efficiency comparable to normal effector cells, during the acute period of AHF, and in early convalescence. Consequently, ADCC can be a relevant mechanism in the clearance of Junin virus-infected cells.