Trypanosoma cruzi dysregulates expression of piRNA that can regulate IL‐6 signaling in human cardiac fibroblasts during the early phase of infection

• Published in: The FASEB journal 2022-05, Vol.36 (S1), p.n/a
• Main Authors: Rayford, Kayla J., Cooley, Ayorinde, Arun, Ashutosh, Rachakonda, Girish, Villalta, Fernando, Lima, Maria F., Pratap, Siddarth, Nde, Pius N.
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.2022.36.S1.R4785

Trypanosoma cruzi, the etiological agent of Chagas Disease, causes severe morbidity, mortality, and economic burden in endemic zones. Due to globalization, the disease is now present in all industrialized regions of the world. About 40% of infected individuals will develop cardiovascular, neurological, and/or gastrointestinal pathologies. Cardiomyopathies induced by chronic parasite infection include organ enlargement and fibrosis, accompanied by significant changes in the cellular expression of profibrotic factors and inflammatory molecules. Accumulating evidence suggests that the parasite induces alterations in host gene expression profiles to facilitate infection and pathogenesis. The role of regulatory gene expression machinery during T. cruzi infection remains to be elucidated. In this study, we aim to evaluate the expression of a class of small non‐coding RNA molecules, piwi‐interacting RNAs (piRNAs), during the early phase of T. cruzi infection in primary human cardiac fibroblasts (PHCF). Recent studies defined a role for STAT3 signaling in the onset of cardiac fibrosis in a Chagasic mouse model. Our bioinformatic analysis of parasite challenged PHCF identified significant modulation of piRNAs targeting IL‐6 signaling pathway components. To validate this, we performed qPCR of IL‐6, SOCS3, and piRNAs predicted to target IL‐6 and SOCS3. Furthermore, we evaluated protein expression for pSTAT3 (Y705) and SOCS3 in cell lysates and IL6 secretion in condition media of parasite challenged PHCF. We observed that the piRNAs expression negatively correlated with their target mRNA and protein expression of IL‐6. This suggests T. cruzi dysregulates the expression of piRNA that can regulate IL‐6 signaling during T. cruzi pathogenesis.