Possible effects of Treponema pallidum infection on human vascular endothelial cells

Abstract

Treponema pallidum belongs to the Spirochaetaceae (spirochetes), ranging from 6 to 15 µm in length, with a diameter of 0.2 µm. It can cause syphilis, a sexually transmitted disease with multiple stages and development that seriously endangers human health, causing 6.3 million new infections each year. 1 Treponema pallidum directly across the mucous membranes of the host or broken skin caused by sexual activity. From a series of previous bioinformatics analyses related to genomics of T. pallidum, it can be seen that T. pallidum lacks a complete biosynthetic pathway, 2,3 which may not satisfy its own needs for survival in the host, so T. pallidum obtains important or essential macromolecules during the infection of host cells. At the same time, the barrier function of the vascular endothelium of the host is destroyed, allowing it to enter the blood and then spread to the distal tissues and organs through flow of blood. 4 Therefore, T. pallidum attaching to and altering host cells (such as endothelial cells) and extracellular matrix are a key initial steps for infection.Treponema pallidum bind to vascular endothelial receptors (unfortunately, the specific receptors are still unknown) by the bacteria adhesion protein (adhesins such as Tp0751, Tp0136, and Tp0155.) (Table 1) to penetrate tissue barriers, such as the intima of vascular endothelium. [5][6][7] It has also been determined that TP0326/Tp92 is a T. pallidum outer membrane protein, and it is presumed that Tp92 also helps T. pallidum attach to host endothelial cells according to the function of homologous protein for mediating cell adhesion. 8 Treponema pallidum then spreads throughout the whole body utilizing blood circulation through tissue and vascular endothelial barriers (e.g., blood-brain barrier and placental barrier), causing multiple organ and tissue infections. 9 However, it

Endothelial dysfunction of syphilis: Pathogenesis

“…51 T. pallidum can degrades the connective matrix of the capillary and the supporting polysaccharide matrix around the blood vessels through the hyaluronic acid enzyme, thereby disrupting the junctions between ECs and alternating the vascular permeability, which may be beneficial for the immediate dissemination of T. pallidum upon entry into the host. 52 In addition, Xu et al 48 found that exosomes derived from T. pallidum-infected macrophages enhanced cell adhesion and permeability, and the levels of the secreted cytokines, including VEGF and IL-8 were higher in the experimental group than in the control group, thereby enhancing the permeability of vascular ECs cultured in vitro. Conversely, it has also been shown that miR-146a-5p, an exosome from T. pallidum-stimulated macrophages, reduces endothelial cell permeability by targeting JAM-C. 53 There has also been evidence that activated platelet secretomes facilitate the adhesion between platelets and endothelial cells, and alter the permeability of blood vessels.…”

“…Multiple reasons contribute to the changes in the permeability of vascular ECs, including secretion of hyaluronidase and inflammation‐related factors, activation of platelets, alterations in the actin cytoskeleton and mediation of the death of ECs 51 . T. pallidum can degrades the connective matrix of the capillary and the supporting polysaccharide matrix around the blood vessels through the hyaluronic acid enzyme, thereby disrupting the junctions between ECs and alternating the vascular permeability, which may be beneficial for the immediate dissemination of T. pallidum upon entry into the host 52 . In addition, Xu et al 48 .…”

Neurosyphilis: insights into its pathogenesis, susceptibility, diagnosis, treatment, and prevention

“…T. pallidum exhibits various effects on host vascular endothelial cells, potentially linked to its invasion of the CNS ( 32 ) (shown in Figure 2 ). Scanning electron microscopy revealed that T. pallidum can directly adhere to human brain microvascular endothelial cells in vitro ( 36 ).…”

Perspectivas atuais da neurossífilis: bases patogênicas, diagnósticas e terapêuticas

“…Brazilian Journal of Implantology and Health Sciences Volume 6, Issue 5 ( 2024), Page 428-439 matriz (MMPs). Bem como exerce múltiplos efeitos sobre as células endoteliais vasculares, principalmente associados à sua penetração no SNC, podendo aderir diretamente às células endoteliais microvasculares (Xie et al, 2022). Ambas as vias de junção intercelular e os mecanismos de endocitose mediados por rafts lipídicos para transpor as barreiras endoteliais foram visulaizados no quadro, contudo, sem comprometer a integridade da barreira (Lithgow et al, 2021).…”