Dendritic Cells Phagocytose and Are Activated byTreponema pallidum

Abstract

Cell-mediated immune processes play a prominent role in the clinical manifestations of syphilis, a sexually transmitted disease of humans caused by spirochetal bacteriumTreponema pallidum. The immune cell type that initiates the early immune response toT. pallidumthus far has not been identified. However, dendritic cells (DCs) are the first immune-competent cells to encounter antigens within skin or mucous membranes, the principal sites of early syphilitic infection. In the present study, immature DC line XS52, derived from murine skin, was utilized to examineT. pallidum-DC interactions and subsequent DC activation (maturation). Electron microscopy revealed thatT. pallidumwas engulfed by DCs via both coiling and conventional phagocytosis and was delivered to membrane-bound vacuoles. The XS52 DC line expressed surface CD14 and mRNA for Toll-like receptors 2 and 4, molecules comprising important signaling components for immune cell activation by bacterial modulins. BothT. pallidumand a synthetic lipopeptide (corresponding to the 47-kDa major membrane lipoprotein) activated the XS52 DC line, as indicated by the secretion of interleukin-12 (IL-12), IL-1β, tumor necrosis factor alpha, and IL-6 and elevated surface expression of CD54. The combined data support the contention that DCs stimulated byT. pallidumand/or its proinflammatory membrane lipoproteins are involved in driving the cellular immune processes that typify syphilis.