The cutaneous response in humans to Treponema pallidum lipoprotein analogues involves cellular elements of both innate and adaptive immunity

To extend prior studies implicating treponemal lipoproteins as major proinf lammatory agonists of syphilitic infection, we examined the responses induc ed by intradermal injection of human subjects with synthetic lipoprotein an alogues (lipopeptides) corresponding to the N termini of the 17- and 47-kDa lipoproteins of Treponema pallidum, Responses were assessed visually and b y flow cytometric analysis of dermal leukocyte populations within fluids as pirated from suction blisters raised over the injection sites. Lipopeptides elicited dose-dependent increases in erythema/induration and cellular infi ltrates. Compared with peripheral blood, blister fluids were highly enriche d for monocytes/macrophages, cutaneous lymphocyte Ag-positive memory T cell s, and dendritic cells. PB and blister fluids contained highly similar rati os of CD123(-)/CD11c(+) (DC1) and CD123(+)/CD11c(-) (DC2) dendritic cells. Staining for maturation/differentiation markers (CD83, CD1a) and costimulat ory molecules (CD80/CD86) revealed that blister fluid DC1, but not DC2, cel ls were more developmentally advanced than their peripheral blood counterpa rts. Of particular relevance to the ability of syphilitic lesions to facili tate the transmission of M-tropic strains of HIV-1 was a marked enhancement of CCR5 positivity among mononuclear cells in the blister fluids. Treponem al lipopeptides have the capacity to induce an inflammatory milieu reminisc ent of that found in early syphilis lesions. In contrast with in vitro stud ies, which have focused upon the ability of these agonists to stimulate iso lated innate immune effector cells, in this study we show that in a complex tissue environment these molecules have the capacity to recruit cellular e lements representing the adaptive as well as the innate arm of the cellular immune response.