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Cyclophilin 19 secreted in the host cell cytosol by Trypanosoma cruzi promotes ROS production required for parasite growth.
- Source :
-
Cellular microbiology [Cell Microbiol] 2021 Apr; Vol. 23 (4), pp. e13295. Date of Electronic Publication: 2020 Dec 09. - Publication Year :
- 2021
-
Abstract
- Infection by Trypanosoma cruzi, the protozoan parasite that causes Chagas disease, depends on reactive oxygen species (ROS), which has been described to induce parasite proliferation in mammalian host cells. It is unknown how the parasite manages to increase host ROS levels. Here, we found that intracellular T. cruzi forms release in the host cytosol its major cyclophilin of 19 kDa (TcCyp19). Parasites depleted of TcCyp19 by using CRISPR/Cas9 gene replacement proliferate inefficiently and fail to increase ROS, compared to wild type parasites or parasites with restored TcCyp19 gene expression. Expression of TcCyp19 in L6 rat myoblast increased ROS levels and restored the proliferation of TcCyp19 depleted parasites. These events could also be inhibited by cyclosporin A, (a cyclophilin inhibitor), and by polyethylene glycol-linked to antioxidant enzymes. TcCyp19 was found more concentrated in the membrane leading edges of the host cells in regions that also accumulate phosphorylated p47 <superscript>phox</superscript> , as observed to the endogenous cyclophilin A, suggesting some mechanisms involved with the translocation process of the regulatory subunit p47 <superscript>phox</superscript> in the activation of the NADPH oxidase enzymatic complex. We concluded that cyclophilin released in the host cell cytosol by T. cruzi mediates the increase of ROS, required to boost parasite proliferation in mammalian hosts.<br /> (© 2020 John Wiley & Sons Ltd.)
- Subjects :
- Animals
Cyclophilins biosynthesis
Cyclophilins genetics
Cytosol chemistry
Myoblasts parasitology
Protozoan Proteins genetics
Protozoan Proteins metabolism
Rats
Trypanosoma cruzi genetics
Cyclophilins metabolism
Cytosol metabolism
Host-Parasite Interactions
Reactive Oxygen Species metabolism
Trypanosoma cruzi growth & development
Trypanosoma cruzi metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1462-5822
- Volume :
- 23
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cellular microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 33222354
- Full Text :
- https://doi.org/10.1111/cmi.13295