Temporal Modulation of Interferon α/γ by LDT409 in Trypanosoma Cruzi-Infected Human Adipocytes ^†

Introduction: Chagas disease (CD) remains a serious public health problem. The currently available pharmacological drugs exhibit limited efficacy during the chronic phase and are associated with significant adverse effects. Consequently, the development of alternative therapies is urgently needed. Compounds derived from cashew nut shell liquid, such as LDT409, which possess anti-inflammatory activity and PPAR-modulating properties, have emerged as promising candidates. This study aimed to evaluate the effect of LDT409 on inflammatory markers over a 15-day period in human adipocytes infected with Trypanosoma cruzi. Methodology: Since adipose tissue is both a target of T. cruzi infection and a site of inflammation during CD progression, we used human mesenchymal stem cells differentiated into adipocytes and infected them with the Y strain of T. cruzi. Treatment with 25 μM LDT409 was initiated 24 h post-infection. RNA was extracted from cells collected on days 3, 7, 10, and 15 for qPCR analysis of IFN-α and IFN-γ gene expression. Results: T. cruzi rapidly infected human adipocytes in vitro. As expected, an increase in IFN-α expression was observed on day 3 in infected cells, with no effect of treatment. By day 10, a downregulation was observed, particularly in infected adipocytes treated with LDT409. On day 15, a reduction in INF-α expression was seen in all experimental groups. In this in vitro adipocyte model without immune cells, IFN-γ expression remained low, regardless of the infection or treatment with the compound. Conclusions: These findings suggest that LDT409 may modulate the inflammatory response in human adipocytes infected with T. cruzi.