DNA damage and oxidative stress in human cells infected by Trypanosoma cruzi

• Published in: PLoS pathogens Vol. 17; no. 4; p. e1009502
• Main Authors: Florentino, Pilar T V, Mendes, Davi, Vitorino, Francisca Nathalia L, Martins, Davi J, Cunha, Julia P C, Mortara, Renato A, Menck, Carlos F M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2021; Public Library of Science (PLoS)
• Subjects: Antioxidants; Antioxidants - metabolism; Biology and Life Sciences; Carbonyls; Care and treatment; Cell cycle; Cell Death; Cell Line; Chagas Disease - parasitology; Chromatin; Damage; Deoxyribonucleic acid; Development and progression; DNA; DNA Damage; DNA Glycosylases - genetics; DNA Glycosylases - metabolism; DNA Repair; Down-Regulation; Enzymes; Flow cytometry; Genetic aspects; Genomes; Genotype; Health aspects; HeLa Cells; Histones - genetics; Histones - metabolism; Host-Parasite Interactions; Humans; Immune response; Immunofluorescence; Infections; Leukocytes (neutrophilic); Macrophages; Mammals; Medicine and Health Sciences; Metabolism; Mitochondrial DNA; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Nuclei; Nuclei (cytology); Oxidative Stress; Parasites; Peroxidase; Phosphorylation; Poly (ADP-Ribose) Polymerase-1 - genetics; Poly (ADP-Ribose) Polymerase-1 - metabolism; Protozoa; Reactive Oxygen Species - metabolism; Research and analysis methods; Transcription; Trypanosoma cruzi - pathogenicity; Trypanosoma cruzi - physiology; Trypanosomiasis; Vector-borne diseases; Brazil; Latin America
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1009502

Trypanosoma cruzi is the etiologic agent of Chagas' disease. Infected cells with T. cruzi activate several responses that promote unbalance of reactive oxygen species (ROS) that may cause DNA damage that activate cellular responses including DNA repair processes. In this work, HeLa cells and AC16 human cardiomyocyte cell line were infected with T. cruzi to investigate host cell responses at genome level during parasites intracellular life cycle. In fact, alkaline sensitive sites and oxidized DNA bases were detected in the host cell genetic material particularly in early stages of infection. These DNA lesions were accompanied by phosphorylation of the histone H2Ax, inducing γH2Ax, a marker of genotoxic stress. Moreover, Poly [ADP-ribose] polymerase-1 (PARP1) and 8-oxoguanine glycosylase (OGG1) are recruited to host cell nuclei, indicating activation of the DNA repair process. In infected cells, chromatin-associated proteins are carbonylated, as a possible consequence of oxidative stress and the nuclear factor erythroid 2-related factor 2 (NRF2) is induced early after infection, suggesting that the host cell antioxidant defenses are activated. However, at late stages of infection, NRF2 is downregulated. Interestingly, host cells treated with glutathione precursor, N-acetyl cysteine, NRF2 activator (Sulforaphane), and also Benznidonazol (BNZ) reduce parasite burst significantly, and DNA damage. These data indicate that the balance of oxidative stress and DNA damage induction in host cells may play a role during the process of infection itself, and interference in these processes may hamper T. cruzi infection, revealing potential target pathways for the therapy support.