Macrophage immune modulation: TGF-β1's influence on IL-1β dynamics in dengue virus infection

• Published in: Revista información científica Vol. 104; p. e4791
• Main Authors: Serrato-Salas, Javier, Ramírez-Agüero, Brenda, Montiel-Hernández, José Luis, González Christen, Judith
• Format: Journal Article
• Language: Portuguese; Spanish
• Published: Universidad de Ciencias Médicas Guantánamo 01.03.2025; Universidad de Ciencias Médicas de Guantánamo
• Subjects: ALLERGY; ANATOMY & MORPHOLOGY; ANESTHESIOLOGY; dengue; HEMATOLOGY; il-1ß; inflammation; innate immunity; macrophage; MEDICINE, GENERAL & INTERNAL; MICROBIOLOGY; NURSING; OBSTETRICS & GYNECOLOGY; ONCOLOGY; ORTHOPEDICS; tgf-ß1; imunidade inata; macrófago; IL-1; macrophage; inflamación; IL-1β; dengue; innate immunity; inflammation; TGF-β1; inflamação; TGF-; inmunidad innata
• ISSN: 1028-9933; 1028-9933
• DOI: 10.5281/zenodo.13741644

RESUMEN Introduction: several pathogenic mechanisms contribute to the severity of dengue virus infection. These include viral cytotoxicity, host genetics, and comorbidities such as diabetes and dyslipidemia. Patients with severe dengue show an uncontrolled immune response with high levels of proinflammatory cytokines (TNF, IL-1β, IL8, IL-6) and chemokines, which damage the microvascular endothelium. Inflammatory cytokines (IL-4, IL-10, TGF-β1) are also increased. The role of TGF-β1in dengue remains unclear. Few studies exist, and most of them use serum data from patients. These suggest both protective and harmful effects. Objective: this study aimed to evaluate how TGF-1β regulates IL-1β secretion in dengue-infected macrophages in vitro; this was carried out in the laboratory of innate immunity, at the Autonomous University of the State of Morelos, Mexico. Method: THP-1 cell line was treated with recombinant TGF-β before or after dengue virus (DENV) infection. Cells were differentiated into macrophages by PMA. Data were obtained by RT-PCR, IFA and ELISA assays. Variables analyzed included IL-1β expression and secretion. Statistical analysis included student t-tests. Results: RT-PCR showed that IL-1β expression was similar in pretreated and control cells. However, IL-1β secretion decreased only when cells were stimulated with TGF-β1 (SB505124) before TGF-β1 treatment and DENV infection abrogated the inhibitory effect of TGF-β1. Conclusions: these findings suggest that DENV might regulate TGF-β1 function in macrophages. Negative regulation of the TGF-β1 pathway is potentially a mechanism by which DENV evades the immune response. This could contribute to immunopathology.