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

Trypanosoma cruzi infection induces DNA double-strand breaks and activates DNA damage response pathway in host epithelial cells

“…Transcriptome analyses of T. cruzi -infected cells revealed modulations in the fatty acid metabolic pathway, immune response, and cellular response to stress 75 – 77 . In addition, several proteins, including PARP-1 and XRRC6 were found upregulated in the host nucleus observed by proteomic analysis 41 . Here, we characterise the activation dynamics of the host key DDR pathway in LLC-MK2 cells, highlighting the initial response to DSB induced by T. cruzi infection.…”

“…In the NHEJ repair complex, DNA-PK is recruited after Ku70/80 heterodimers to stabilize broken DNA strands 56 , 83 . It has been shown during T. cruzi infection that Ku70 is increased in the nucleus at 6 hpi 41 . Together, our findings provide evidence that the assembly of the NHEJ complex, occurring between 6 and 12 hpi, then initiates the restoration of host DNA integrity.…”

“…The correct orchestration of this pathway is crucial to maintain the genome integrity and allows cells to continue cell cycle progression and survive. It has been reported that infection by T. cruzi causes alterations in the host chromatin, affecting the host genome stability 40 , 41 . However, the activation dynamics of the key proteins of the DDR pathway have yet to be well studied during T. cruzi infection.…”

PARPs and ADP-Ribosylation in Chronic Inflammation: A Focus on Macrophages

“…Activity Disease/Biological Process(s) PARP1/ARTD1 PARylation, MARylation, or non-catalytic activity Emphysema/Chronic lung inflammation [49,50] H. pylori infection [51] Colitis/Inflammatory bowel diseases [53,54,56] Psoriasis [57,66] Atopic dermatitis [58] Alcoholic liver injury [63] Chagas heart disease [69][70][71][72] PARP7/ARTD14 MARylation SARS-CoV-2 infection [23] Colitis/Inflammatory bowel diseases [53,54,56] PARP9/ARTD9 MARylation Pulmonary tuberculosis [83,84] RNA-viruses infections [85,86] Atherosclerosis/arterial inflammation [79,80] SARS-CoV-2 infection [117] PARP10/ARTD10 MARylation SARS-CoV-2 infection [23] Arboviruses infections [88] PARP12/ARTD12 MARylation Assembly and maintenance of stress granules [15] SARS-CoV-2 infection [23] PARP13/ARTD13 Non-catalytic activity Assembly and maintenance of stress granules [15] Atherosclerosis/arterial inflammation [79,80,90,91] Arboviruses infections [88,89] PARP15/ARTD7 MARylation Assembly and maintenance of stress granules [15] Arboviruses infections [88] PARG Hydrolysis (PAR) Assembly and maintenance of stress granules [15,98] Macrodomain 1 (nsp3) Hydrolysis (MAR) SARS-CoV-2 infection …”

“…Further evidence indicated that depletion of PARP1/ARTD1 (with genetic deletion or PJ-34 administration) in infected mice prevented cardiac hypertrophy and left ventricle dysfunction and restored the mitochondrial antioxidant/oxidant balance [ 70 ]. PARP1/ARTD1 is associated with chromatin during T. cruzi infection but its mRNA levels did not change when compared to non-infected states, indicating that a translocation of PARP1/ARTD1 to chromatin-dense regions occurred [ 71 , 72 ]. These results suggest that PARP1/ARTD1 influences the response to mitochondrial stress during T. cruzi infection.…”