Vitamin D-induced LL-37 modulates innate immune responses of human primary macrophages during DENV-2 infection

ABSTRACT: Epidemics of dengue, an acute and potentially severe disease caused by mosquito-borne dengue virus (DENV), pose a major challenge to clinicians and health care services across the sub(tropics). Severe disease onset is associated with a dysregulated inflammatory response to the virus, and there are currently no drugs to alleviate disease symptoms. LL-37 is a potent antimicrobial peptide with a wide range of immunoregulatory properties. In this study, we assessed the effect of LL-37 on DENV-2-induced responses in human monocyte-derived macrophages (MDMs). We show that simultaneous exposure of exogenous LL-37 and DENV-2 resulted in reduced replication of the virus in MDMs, while the addition of LL-37 postexposure to DENV-2 did not. Interestingly, the latter condition reduced the production of IL-6 and increased the expression of genes involved in virus sensing and antiviral response. Finally, we demonstrate that low endogenous levels and limited production of LL-37 in MDMs in response to DENV-2 infection can be increased by differentiating MDMs in the presence of Vitamin D (VitD3). Taken together, this study demonstrates that in addition to its antimicrobial properties, LL-37 has immunomodulatory properties in the curse of DENV infection and its production can be increased by VitD3.

• Autores: Castillo Ramírez, Jorge Andrés; Giraldo Giraldo, Diana Marcela; Rodenhuis Zybert, Izabela Agata; Smit, Jolanda; Urcuqui Inchima, Silvio
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2022
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/29734
• Acceso en línea: https://hdl.handle.net/10495/29734
• Palabra clave: Virus del Dengue; Dengue Virus; Macrófagos; Macrophages; Inmunidad Innata; Immunity, Innate; Vitamina D; Vitamin D; LL-37
• Rights: openAccess
• License: Atribución-NoComercial-CompartirIgual 2.5 Colombia