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

Jorge Andrés Castillo, Diana Marcela Giraldo, Jolanda M Smit, Izabela A Rodenhuis-Zybert, Silvio Urcuqui-Inchima*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article numberftac014
Number of pages11
JournalPathogens and Disease
Volume80
Issue number1
DOIs
Publication statusE-pub ahead of print - 5-May-2022

Keywords

  • Animals
  • Dengue
  • Dengue Virus
  • Humans
  • Immunity, Innate
  • Macrophages
  • Virus Replication
  • Vitamin D/metabolism

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