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Human β-defensin 2 is involved in CCR2-mediated Nod2 signal transduction, leading to activation of the innate immune response in macrophages

Authors
  • Kim, Ju1
  • Yang, Ye Lin2
  • Jang, Yong-Suk1, 2
  • 1 Department of Molecular Biology and the Institute for Molecular Biology and Genetics, Chonbuk National University, 54896, South Korea
  • 2 Department of Bioactive Material Sciences and Institute of Bioactive Materials, Chonbuk National University, Jeonju, 54856, South Korea
Type
Published Article
Journal
Immunobiology
Publisher
Elsevier GmbH.
Publication Date
May 18, 2019
Volume
224
Issue
4
Pages
502–510
Identifiers
DOI: 10.1016/j.imbio.2019.05.004
PMID: 31126693
PMCID: PMC7114636
Source
PubMed Central
Keywords
Disciplines
  • Article
License
Unknown

Abstract

Beta-defensins contribute to host innate defense against various pathogens, including viruses, although the details of their roles in innate immune cells are unclear. We previously reported that human β-defensin 2 (HBD 2) activates primary innate immunity against viral infection and suggested that it plays a role in the induction of the adaptive immune response. We analyzed the mechanisms by which HBD 2 primes innate antiviral immunity and polarized activation of macrophage-like THP-1 cells using the receptor-binding domain (RBD) of Middle East respiratory syndrome coronavirus (MERS-CoV) spike protein (S RBD) as a model antigen. The expression of nucleotide-binding oligomerization domain containing 2 (Nod2), type I interferons, (IFNs), and proinflammatory mediators was enhanced in S RBD-HBD 2-treated THP-1 cells. S RBD-HBD 2 treatment also enhanced phosphorylation and activation of receptor-interacting serine/threonine-protein kinase 2 and IFN regulatory factor 3 compared to S RBD alone. Finally, HBD 2-conjugated S RBD interacted with C-C chemokine receptor 2 (CCR2), and Nod2 was involved in HBD 2-mediated CCR2 signaling, which was associated with the activation and M1 polarization of THP-1 cells. Therefore, HBD 2 promotes CCR2-mediated Nod2 signaling, which induces production of type I IFNs and an inflammatory response, and enhances primary innate immunity leading to an effective adaptive immune response to HBD 2-conjugated antigen.

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