Interaction of Treponema pallidum, the syphilis spirochete, with human platelets

Abstract

Extracellular bacteria that spread via the vasculature employ invasive mechanisms that mirror those of metastatic tumor cells, including intravasation into the bloodstream and survival during hematogenous dissemination, arrestation despite blood flow, and extravasation into distant tissue sites. Several invasive bacteria have been shown to exploit normal platelet function during infection. Due to their inherent ability to interact with and influence other cell types, platelets play a critical role in alteration of endothelial barrier permeability, and their role in cancer metastasis has been well established. The highly invasive bacterium and causative agent of syphilis, Treponema pallidum subspecies pallidum, readily crosses the endothelial, blood-brain and placental barriers. However, the mechanisms underlying this unusual and important aspect of T. pallidum pathogenesis are incompletely understood. In this study we use darkfield microscopy in combination with flow cytometry to establish that T. pallidum interacts with platelets. We also investigate the dynamics of this interaction and show T. pallidum is able to activate platelets and preferentially interacts with activated platelets. Platelet-interacting treponemes consistently exhibit altered kinematic (movement) parameters compared to free treponemes, and T. pallidum-platelet interactions are reversible. This study provides insight into host cell interactions at play during T. pallidum infection and suggests that T. pallidum may exploit platelet function to aid in establishment of disseminated infection.

Increased CCL24 and CXCL7 levels in the cerebrospinal fluid of patients with neurosyphilis

“…This may suggest that the increased numbers of nucleated cells in the CSF of patients with neurosyphilis may be due to the continuous damage of the vascular endothelial cells of the blood‐brain barrier, rather than due to the direct chemotaxis of monocytes. Interestingly, Church et al reported that T pallidum directly, preferentially, and reversibly interact with activated platelets, alter their movement and blood‐brain barrier permeability, eventually facilitating their dissemination 38 . The increased CSF levels of CCL24, CXCL7, and CXCL8 require further investigation to elucidate the role of eosinophils and neutrophils in neurosyphilis.…”

A Rare Case of an Abdominal Aortic Thrombus Secondary to Syphilitic Aortitis

“…Approximately ⅓ of patients with untreated syphilis present with tertiary syphilis 10-30 years following initial exposure, and while rare, thrombosis of the aorta has been reported in syphilitic aortitis, a sequela of the tertiary disease [9]. Recent research studying Treponema pallidum has revealed that it is an invasive bacteria with the ability to readily cross-endothelial barriers through its ability to interact with, and activate platelets [10]. While further research is needed to expound upon these results and to elucidate the mechanisms behind mural thrombus formation in syphilitic aortitis, it aids in explaining the development of thrombosis in the absence of atherosclerosis.…”

Emerging Nano-Carrier Strategies for Brain Tumor Drug Delivery and Considerations for Clinical Translation

“…Common receptors in pathogen transcytosis-based brain entry are the transferrin receptor, insulin receptor and LRP1/LRP2. Treponema pallidum , the causative agent of syphilis, interacts with platelets, allowing it to cross the BBB as well as the placental and retinal barriers [ 111 ]. Using an approach inspired by Cryptococcus neoformans , a cause of fungal meningitis, Aaron and Gelli used a secreted fungal metalloprotease, Mpr1, as a means of increasing quantum dot penetration through an in vitro BBB model [ 112 ].…”