Archaea Symbiont of T. cruzi Infection May Explain Heart Failure in Chagas Disease

Background: Archaeal genes present in Trypanosoma cruzi may represent symbionts that would explain development of heart failurein 30% of Chagas' diseasepatients. Extracellular vesiclesin peripheral blood, called exosomes(0.1μm), present in larger numbers in heart failure, were analyzed to determine whether they are derived from archaeain heart failure Chagas' disease. Methods: Exosomesand microvesiclesin serum supernatant from 3 groups were analyzed: heart failure Chagas' disease(N= 26), asymptomatic indeterminate form(N= 21) and healthy non chagasic control (N= 16). Samples were quantified with transmission electron microscopy, flow cytometer immunolabeledwith anti-archaemetzincin-1 antibody (AMZ 1, archaea collagenase) and probe anti-archaeal DNA and zymographyto determine AMZ1 (Archaeal metalloproteinase) activity. Results: Indeterminate formpatients had higher median numbers of exosomes/case versus heart failurepatients (58.5 vs 25.5, P<0.001), higher exosomecontent of AMZ1 antigens (2.0 vs 0.0; P<0.001), and lower archaeal DNA content (0.2 vs 1.5, P=0.02). A positive correlation between exosomesand AMZ1 content was seen in indeterminate form(r=0.5, P<0.001), but not in heart failurepatients (r=0.002, P=0.98). Higher free archaeal DNA (63.0 vs 11.1, P<0.001) in correlation with exosomenumbers (r=0.66, P=0.01) was seen in heart failurebut not in indeterminate form(r=0.29, P=0.10). Flow cytometer showed higher numbers of AMZ1 microvesiclesin indeterminate form(64 vs 36, P=0.02) and higher archaeal DNA microvesiclesin heart failure(8.1 vs 0.9, P<0.001). Zymographyshowed strong % collagenaseactivity in HF group, mild activity in IF compared to non chagasic healthy group (121 ± 14, 106 ± 13 and 100) (P <0.001). Conclusions: Numerous exosomes, possibly removing and degrading abnormal AMZ1 collagenase, are associated with indeterminate form. Archaeal microvesiclesand their exosomes, possibly associated with release of archaeal AMZ1 in heart failure, are future candidates of heart failurebiomarkers if confirmed in larger series, and the therapeutic focus in the treatment of Chagas disease.