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

Autor:	Castillo JA; Grupo Inmunovirología. Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, 050010, Colombia.; Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen , The Netherlands., Giraldo DM; Grupo Inmunovirología. Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, 050010, Colombia., Smit JM; Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen , The Netherlands., Rodenhuis-Zybert IA; Department of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen , The Netherlands., Urcuqui-Inchima S; Grupo Inmunovirología. Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia UdeA, Calle 70 No 52-21, Medellín, 050010, Colombia.
Jazyk:	angličtina
Zdroj:	Pathogens and disease [Pathog Dis] 2022 May 23; Vol. 80 (1).
DOI:	10.1093/femspd/ftac014
Abstrakt:	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. (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)
Databáze:	MEDLINE
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