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

ABSTRACT: Chagas disease is endemic in 22 Latin American countries, with approximately 8 million individuals infected worldwide and 10,000 deaths per year. Trypanosoma cruzi, the etiologic agent from Chagas disease, 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 the early and late stages of infection. To further understand changes in host cell chromatin induced by parasite infection, we investigated proteomic alterations in chromatin caused by parasite infection at early and late infection phases by performing a quantitative proteomic analysis. Interestingly, we identified DNA Damage Repair (DDR) proteins recruited to the chromatin and changes in chromatin remodeling enzymes, suggesting that parasite infection may shape the epigenome of the host cells. Furthermore, the presence of Poly-ADP-ribose Polymerase 1 (PARP-1) and 8-oxoG Glycosylase (OGG1) in the host nucleus confirm the damaged cellular genome. Moreover, we observed that at 6 h post-infection, PARP-1 and X-Ray Repair Cross Complementing 6 (XRRC6) were upregulated in the chromatin of infected cells. Interestingly, mitochondrial proteins involved in oxidative phosphorylation and vesicle-mediated transport proteins were upregulated in the host chromatin at the final stages of infection. Additionally, we have observed that Apoptosis-inducing Factor (AIF) is translocated to the host cell nucleus upon infection, suggesting that cells enter parthanatos type of death. Finally, we also observed that T. cruzi induces changes in chromatin-modifying enzymes. Altogether, this work provides novel data reveals how parasites interfere in the host cells' responses at the chromatin level and important crosstalks that support and disseminate infection.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hela Cell

SUBMITTER: Julia Cunha  

LAB HEAD: Carlos Frederico Martins Mendes

PROVIDER: PXD033862 | Pride | 2024-09-28

REPOSITORIES: Pride