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 t...
- 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
| Summary: | 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. |
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