Journal Article

Modulation of miR-145-5p and miR-146b-5p levels is linked to reduced parasite load in H9C2 Trypanosoma cruzi infected cardiomyoblasts

Moreira, Otacilio Cruz, Gibaldi, Daniel, Ferreira, Beatriz Iandra Silva, Lannes-Vieira, Joseli, Farani, Priscila Silva Grijó

2022

Overview

In the heart tissue of acutely Trypanosoma cruzi -infected mice miR-145-5p and miR-146b-5p are, respectively, downregulated and upregulated. Here, we used the H9C2 rat cardiomyoblast cell line infected with the Colombian T. cruzi strain to investigate the parasite-host cell interplay, focusing on the regulation of miR-145-5p and miR-146b-5p expression. Next, we explored the effects of interventions with the trypanosomicidal drug Benznidazole (Bz) alone or combined with Pentoxifylline (PTX), a methylxanthine derivative shown to modulate immunological and cardiac abnormalities in a model of chronic chagasic cardiomyopathy, on parasite load and expression of miR-145-5p and miR-146b-5p. The infection of H9C2 cells with trypomastigote forms allowed parasite cycle with intracellular forms multiplication and trypomastigote release. After 48 and 144 h of infection, upregulation of miR-145-5p (24 h: 2.38 ± 0.26; 48 h: 3.15 ± 0.9-fold change) and miR-146b-5b (24 h: 2.60 ± 0.46; 48 h: 2.97 ± 0.23-fold change) was detected. The peak of both miRNA levels paralleled with release of trypomastigote forms. Addition of 3 µM and 10 µM of Bz 48 h after infection reduced parasite load but did not interfere with miR-145-5p and miR-146b-5p levels. Addition of PTX did not interfere with Bz-induced parasite control efficacy. Conversely, combined Bz + PTX treatment decreased the levels of both microRNAs, resembling the expression levels detected in non-infected H9C2 cells. Moreover, the use of miR-145-5p and miR-146b-5p mimic/inhibitor systems before infection of H9C2 cells decreased parasite load, 72 h postinfection. When H9C2 cells were treated with miR-145-5p and miR-146b-5p mimic/inhibitor 48 h after infection, all the used systems, except the miR-146b-5p inhibitor, reduced parasite load. Altogether, our data indicate that these microRNAs putatively control signaling pathways crucial for parasite–host cell interaction. Thus, miR-145-5p and miR-146b-5p deserve to be further investigated as biomarkers of parasite control and tools to identify therapeutic adjuvants to etiological treatment in Chagas disease.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/326/417/2546 / 631/80/304 / Adjuvants / Animals / Benznidazole / Cardiomyopathy / Cell Line / Chagas disease / Dose-Response Relationship, Drug / Drug Combinations / Gene Expression Regulation / Host-parasite interactions / Host-Parasite Interactions - drug effects / Host-Parasite Interactions - genetics / Humanities and Social Sciences / Infections / MicroRNAs / MicroRNAs - antagonists & inhibitors / MicroRNAs - genetics / MicroRNAs - metabolism / miRNA / multidisciplinary / Myocytes, Cardiac - drug effects / Myocytes, Cardiac - metabolism / Myocytes, Cardiac - parasitology / Nitroimidazoles - pharmacology / Oligoribonucleotides - genetics / Oligoribonucleotides - metabolism / Parasite control / Parasites / Pentoxifylline - pharmacology / Rats / Science / Science (multidisciplinary) / Signal Transduction / Trypanocidal Agents - pharmacology / Trypanosoma cruzi / Trypanosoma cruzi - drug effects / Trypanosoma cruzi - genetics / Trypanosoma cruzi - growth & development / Vector-borne diseases