Treponema pallidum elicits innate and adaptive cellular immune responses in skin and blood during secondary syphilis: a flow-cytometric analysis

J Infect Dis. 2007 Mar 15;195(6):879-87. doi: 10.1086/511822. Epub 2007 Feb 5.


Background: Syphilis is caused by the spirochetal pathogen Treponema pallidum. The local and systemic cellular immune responses elicited by the bacterium have not been well studied in humans.

Methods: We used multiparameter flow cytometry to characterize leukocyte immunophenotypes in skin and peripheral blood from 23 patients with secondary syphilis and 5 healthy control subjects recruited in Cali, Colombia. Dermal leukocytes were obtained from fluid aspirated from epidermal suction blisters raised over secondary syphilis skin lesions.

Results: Compared with peripheral blood (PB), blister fluids (BFs) were enriched for CD4(+) and CD8(+) T cells, activated monocytes/macrophages, and CD11c(+) monocytoid and CD11c(-) plasmacytoid dendritic cells (mDCs and pDCs, respectively). Nearly all mDCs in BFs expressed the human immunodeficiency virus (HIV) coreceptors CCR5 and DC-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) and high levels of human leukocyte antigen (HLA)-DR. Dermal pDCs expressed both HIV coreceptors without increases in HLA-DR intensity. Compared with normal blood, circulating mDCs in patients with syphilis expressed higher levels of both CCR5 and DC-SIGN, whereas circulating pDCs in patients expressed only higher levels of DC-SIGN. Most dermal T cells were CCR5(+) and displayed a memory (CD27(+)/CD45RO(+)) or memory/effector (CD27(-)/CD45RO(+)) immunophenotype. A corresponding shift toward memory and memory/effector immunophenotype was clearly discernible among circulating CD4(+) T cells. Compared with PB from control subjects, a larger percentage of CD4(+) T cells in PB from patients with syphilis expressed the activation markers CD69 and CD38.

Conclusions: During secondary syphilis, T. pallidum simultaneously elicits local and systemic innate and adaptive immune responses that may set the stage for the bidirectional transmission of HIV.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antigens, CD / blood
  • Antigens, CD / immunology
  • Blister / immunology
  • Blister / microbiology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Dendritic Cells / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunity, Cellular*
  • Immunity, Innate*
  • Immunophenotyping
  • Male
  • Middle Aged
  • Skin / immunology
  • Skin / microbiology
  • Syphilis / immunology*
  • Treponema pallidum / immunology*


  • Antigens, CD