Recombinant ferritin nanoparticles can induce dendritic cell maturation through TLR4/NF-κB pathway

  • Biotechnol Lett. 2020 Dec;42(12):2489-2500. doi: 10.1007/s10529-020-02944-8.
Zhehui Qu  1  2 ,  Yongli Guo  3 ,  Mingzhu Li  1 ,  Chong Cao  1 ,  Junwei Wang  4 ,  Mingchun Gao  5
Affiliations
  • 1. Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, 150030, Heilongjiang, People's Republic of China.
  • 2. College of Animal Science and Veterinary Medicine, Xinyang Agriculture and Forestry University, Xinyang, 464000, Henan, People's Republic of China.
  • 3. Animal Disease Prevention and Control Center of Heilongjiang Province, Harbin, 150069, Heilongjiang, People's Republic of China.
  • 4. Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, 150030, Heilongjiang, People's Republic of China. [email protected].
  • 5. Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Xiangfang District, Harbin, 150030, Heilongjiang, People's Republic of China. [email protected].
PMID: 32567013 DOI: 10.1007/s10529-020-02944-8
Abstract

Objective: Immune response initiation and regulation require activation of dendritic cells (DCs). However, the mechanism by which ferritin, a carrier for immunogen, induces DCs maturation remains unclear.

Results: Recombinant ferritin nanoparticle (RFNp), were prepared through the baculovirus expression vector system, formed spherical and hollow cage-liked proteins with a diameter of approximately 12.17 ± 0.87 nm. They induced bone marrow-derived DC (BMDC) maturation via surface molecules up-regulation of (MHC II, CD80, CD86 and CD40), increased pro-inflammatory cytokines production (IL-6, IL-12, TNF-α, and IFN-γ), and decreased antigen capturing capacity. They positively regulated IκBα and NF-κB (p65) phosphorylation, and facilitate NF-κB (p65) translocation into mature BMDCs nuclei. Following pre-treatment of RFNp-treated BMDCs with TLR4 and NF-κB (p65) inhibitors, respectively, surface molecule expression, pro-inflammatory cytokines production, and IκBα and NF-κB (p65) activities were suppressed. RFNp-treated BMDCs can also facilitate T-cell proliferation and differentiation into Th1 and Th2.

Conclusion: RFNps induced DCs maturation lends the potential application of RFNps as carrier platforms in DC-based vaccine.

Keywords
Dendritic cell; Maturation; Recombinant ferritin nanoparticle; T lymphocytes; TLR4/NF-κB.
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