The role of the 47-kDa membrane lipoprotein of Treponema pallidum in promoting maturation of peripheral blood monocyte-derived dendritic cells without enhancing C-C chemokine receptor type 7-mediated dendritic cell migration

Adv Clin Exp Med. 2023 Mar;32(3):369-377. doi: 10.17219/acem/154857.

Abstract

Background: The 47-kDa membrane lipoprotein (Tp47) is the most representative membrane protein of Treponema pallidum (T. pallidum). Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) that connect innate and acquired immunity. The regulatory role of Tp47 on DCs remains unclear.

Objectives: To evaluate the effects of Tp47 on DC maturation and migration, and research the changes of the main chemokine C-C chemokine receptor type 7 (CCR7) involved in DC migration.

Material and methods: A transwell assay was applied to assess the migration of DCs. Cytokines (interleukin (IL)-6, IL-10, IL-12, and tumor necrosis factor alpha (TNF-α)) in the supernatants were measured using enzyme-linked immunosorbent assay (ELISA), and the expression of cell surface markers (CD80, CD86, CD40, and human leukocyte antigen (HLA)-DR) and CCR7 was assessed using flow cytometry. The expression of CCR7 in DCs was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR).

Results: The Tp47 promoted DC phenotypic maturation, such as increased CD40, CD80, CD86, and HLA-DR expression, as well as DC functional maturation, thus stimulating DCs to secrete inflammatory cytokines, including IL-6, IL-10, IL-12, and TNF-α. At the same time, Tp47 did not enhance DC migration and did not increase the expression of CCR7.

Conclusions: The Tp47 promoted the maturation of DCs while not enhancing CCR7-mediated DC migration ability. This may be one of the mechanisms by which T. pallidum escapes host immune clearance.

Keywords: C-C chemokine receptor type 7; Treponema pallidum; dendritic cells; migration; syphilis.

MeSH terms

  • CD40 Antigens / metabolism
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Cytokines / metabolism
  • Dendritic Cells / metabolism
  • Humans
  • Interleukin-10* / metabolism
  • Interleukin-12 / metabolism
  • Monocytes / metabolism
  • Receptors, CCR7 / metabolism
  • Treponema pallidum / metabolism
  • Tumor Necrosis Factor-alpha* / metabolism

Substances

  • Interleukin-10
  • Tumor Necrosis Factor-alpha
  • Receptors, CCR7
  • Cytokines
  • Interleukin-12
  • CD40 Antigens