Introduction Syphilis is a multi-stage, sexually transmitted disease caused by the spirochete Treponema pallidum (Tp). Clinical manifestations result from the treponeme’s ability to elicit a robust immune response while at the same time evading host defenses. Syphilitic lesions are comprised of a rich cellular infiltrate, which includes IFN-gamma (IFNg) producing T cells, NK cells and activated macrophages. We previously, we demonstrated that human syphilitic serum (HSS) promotes efficient uptake of Tp by human monocytes and that opsonophagocytosis of Tp markedly enhances cytokine production. The purpose of this study is to establish a potential role for macrophages and opsonic Ab in clearance of Tp and generation of tissue-based inflammation during human syphilis.
Methods We used monocyte-derived macrophages to develop an ex vivo model for studying spirochete-macrophage interactions. We used macrophage-colony stimulating factor and IFNg for macrophage maturation and evaluated the immunophenotypic modulations by flow cytometry. We assessed Tp uptake, in the presence or absence of HSS by confocal microscopy. We also determined the cellular responses initiated by opsonophagocytosis of Tp using targeted transcriptional array analysis and cytokine bead array.
Results IFNg polarisation of macrophages led to an increase in Fcg receptors (FcgRs) expression, phagocytosis of HSS opsonized Tp and cytokine production. Blockade of CD64 significantly diminished spirochetal uptake and pro-inflammatory cytokine secretion by the macrophages.
Conclusion Our ex vivo studies provide a potential role for macrophages in clearance of Tp during human syphilis. These data are the first to demonstrate that CD64 in the primary FcR involved in opsonophagocytosis of Tp and IFNg plays a critical role in the macrophages responsiveness following uptake of the spirochete. Moreover, our study results also provide an ex vivo surrogate system for use in future syphilis vaccine studies.
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