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

Abstract

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. © 2007 by the Infectious Diseases Society of America. All rights reserved.