Abstract
Trypanosoma cruzi proliferate and differentiate inside different compartments of triatomines gut that is the first environment encountered by T. cruzi. Due to its complex life cycle, the parasite is constantly exposed to reactive oxygen species (ROS). We tested the influence of the pro-oxidant molecules H2O2 and the superoxide generator, Paraquat, as well as, metabolism products of the vector, with distinct redox status, in the proliferation and metacyclogenesis. These molecules are heme, hemozoin and urate. We also tested the antioxidants NAC and GSH. Heme induced the proliferation of epimastigotes and impaired the metacyclogenesis. β-hematin, did not affect epimastigote proliferation but decreased parasite differentiation. Conversely, we show that urate, GSH and NAC dramatically impaired epimastigote proliferation and during metacyclogenesis, NAC and urate induced a significant increment of trypomastigotes and decreased the percentage of epimastigotes. We also quantified the parasite loads in the anterior and posterior midguts and in the rectum of the vector by qPCR. The treatment with the antioxidants increased the parasite loads in all midgut sections analyzed. In vivo, the group of vectors fed with reduced molecules showed an increment of trypomastigotes and decreased epimastigotes when analyzed by differential counting. Heme stimulated proliferation by increasing the cell number in the S and G2/M phases, whereas NAC arrested epimastigotes in G1 phase. NAC greatly increased the percentage of trypomastigotes. Taken together, these data show a shift in the triatomine gut microenvironment caused by the redox status may also influence T. cruzi biology inside the vector. In this scenario, oxidants act to turn on epimastigote proliferation while antioxidants seem to switch the cycle towards metacyclogenesis. This is a new insight that defines a key role for redox metabolism in governing the parasitic life cycle.
Highlights
The parasitic protozoan Trypanosoma cruzi, which is responsible for Chagas disease [1], presents four distinct stages in its complex life cycle
In order to evaluate the effect of a pro-oxidant milieu upon epimastigotes growth, we challenged the parasites with two classical oxidants: H2O2 (Fig. 1A) and the well-known superoxide generator, Paraquat (Fig. 1B)
We evaluated the effect of physiological molecules present in different compartments of the invertebrate vector on epimastigote growth
Summary
The parasitic protozoan Trypanosoma cruzi, which is responsible for Chagas disease [1], presents four distinct stages in its complex life cycle. In the rectum of the vector, a new differentiation (metacyclogenesis) takes place, where epimastigotes transform into non-proliferative, infective metacyclic trypomastigotes. These metacyclic trypomastigotes are released along with the feces and urine of the insect and may reach the bloodstream of a new vertebrate host, where they infect mainly macrophages or cardiac and smooth muscle fibers. In these cells, the parasite undergoes another dramatic transformation into proliferative intracellular amastigotes. After intense multiplication inside the host cell, the amastigotes become bloodstream trypomastigotes that can infect other host cells or reach the circulatory system, completing the cycle [2, 3]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
