Trypanosoma cruzi infection changes the chromatin proteome profile of infected human cells.

Autor: Florentino PTV; Dept. of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Vitorino FNL; Laboratory of Cell Cycle, Butantan Institute, São Paulo, Brazil; Center of Toxins, Immune Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, Brazil. Electronic address: francisca.nathalia.lv@gmail.com., Mendes D; Dept. of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., da Cunha JPC; Laboratory of Cell Cycle, Butantan Institute, São Paulo, Brazil; Center of Toxins, Immune Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo, Brazil., Menck CFM; Dept. of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: cfmmenck@usp.br.
Jazyk: angličtina
Zdroj: Journal of proteomics [J Proteomics] 2023 Feb 10; Vol. 272, pp. 104773. Date of Electronic Publication: 2022 Nov 19.
DOI: 10.1016/j.jprot.2022.104773
Abstrakt: Chagas disease is endemic in 22 Latin American countries, with approximately 8 million individuals infected worldwide and 10,000 deaths yearly. Trypanosoma cruzi presents an intracellular life cycle in mammalian hosts to sustain infection. Parasite infection activates host cell responses, promoting an unbalance in reactive oxygen species (ROS) in the intracellular environment inducing genomic DNA lesions in the host cell during infection. To further understand changes in host cell chromatin induced by parasite infection, we investigated alterations in chromatin caused by infection by performing quantitative proteomic analysis. DNA Damage Repair proteins, such as Poly-ADP-ribose Polymerase 1 (PARP-1) and X-Ray Repair Cross Complementing 6 (XRRC6), were recruited to the chromatin during infection. Also, changes in chromatin remodeling enzymes suggest that parasite infection may shape the epigenome of the host cells. Interestingly, the abundance of oxidative phosphorylation mitochondrial and vesicle-mediated transport proteins increased in the host chromatin at the final stages of infection. In addition, Apoptosis-inducing Factor (AIF) is translocated to the host cell nucleus upon infection, suggesting that cells enter parthanatos type of death. Altogether, this study reveals how parasites interfere with the host cells' responses at the chromatin level leading to significant crosstalk that support and disseminate infection. SIGNIFICANCE: The present study provides novel insights into the effects of Trypanosoma cruzi on the chromatin from the host cell. This manuscript investigated proteomic alterations in chromatin caused by parasite infection at early and late infection phases by performing a quantitative proteomic analysis. In this study, we revealed that parasites interfere with DNA metabolism in the early and late stages of infection. We identified that proteins related to DNA damage repair, oxidative phosphorylation, and vesicle-mediated transport have increased abundance at the host chromatin. Additionally, we have observed that Apoptosis-inducing Factor is translocated to the host cell nucleus upon infection, suggesting that the parasites could lead the cells to enter Parthanatos as a form of programmed cell death. The findings improve our understanding on how the parasites modulate the host cell chromatin to disseminate infection. In this study, we suggest a mechanistic parasite action towards host nucleus that could be used to indicate targets for future treatments.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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