Host Defense Mechanisms in Secondary Syphilitic Lesions

Abstract

Although known for many centuries, the exact pathomechanisms in the course of syphilis are still unknown. Cell-mediated immunity is thought to be of critical importance in anti-syphilitic host defense, but the detailed cellular players leading to the elimination of Treponema pallidum are elusive. This is particularly true for HIV-infected persons, where severe clinical manifestations and therapy failures are more common than in HIV-seronegative individuals. We therefore obtained lesional skin samples from HIV+ and HIV- patients with secondary syphilis at different time points of lesional age to search for the causative microorganisms and to characterize the inflammatory infiltrate. By doing so, we detected T. pallidum spirochetes with a much greater abundance in late lesions of HIV+ individuals as compared to the HIV- cohort. The dominating inflammatory cells were T-cells, macrophages and neutrophils in all stages and plasma cells in older lesions. In HIV- persons, T-cells consisted of equal numbers of CD4+ and CD8+ T-cells, whereas in HIV+ patients the majority of T-cells belonged to the CD8 lineage and produced IFN- and IL-17. Regulatory T-cells and Langerhans cells were reduced in these patients as compared to their HIV- counterparts. On the basis of our observations, we propose that T-cells of both the CD4 and CD8 lineage are needed for an at least partly protective anti-syphilitic immunity. Compensation mechanisms in HIV+ individuals such as an increase of Tc1/17 cells as well as a reduction in immunoregulatory Langerhans cells and T-cells do apparently not overcome these patients' deficiency to eliminate the spirochete.