Crossing the Barrier: A Comparative Study of Listeria monocytogenes and Treponema pallidum in Placental Invasion

Abstract

Vertically transmitted infections are a significant cause of fetal morbidity and mortality during pregnancy and pose substantial risks to fetal development. These infections are primarily transmitted to the fetus through two routes: (1) direct invasion and crossing the placenta which separates maternal and fetal circulation, or (2) ascending the maternal genitourinary tact and entering the uterus. Only two bacterial species are commonly found to cross the placenta and infect the fetus: Listeria monocytogenes and Treponema pallidum subsp. pallidum. L. monocytogenes is a Gram-positive, foodborne pathogen found in soil that acutely infects a wide variety of mammalian species. T. pallidum is a sexually transmitted spirochete that causes a chronic infection exclusively in humans. We briefly review the pathogenesis of these two very distinct bacteria that have managed to overcome the placental barrier and the role placental immunity plays in resisting infection. Both organisms share characteristics which contribute to their transplacental transmission. These include the ability to disseminate broadly within the host, evade immune phagocytosis, and the need for a strong T cell response for their elimination.

Keywords: Listeria monocytogenes; Treponema pallidum; congenital syphilis; pregnancy; syphilis; vertical transmission.

Figure 1

Placental inflammation leads to loss of fetal tolerance. During normal development, placental Hofbauer cells, trophoblasts, and Tregs prevent the development of anti-fetal immunity. These cells maintain the production of tolerogenic factors even during infection with L. monocytogenes. However, a sufficiently severe infection eventually leads to increased proinflammatory cytokines, transition of Hofbauer cells towards an M1 phenotype, and an influx of innate immune cells. These processes culminate in loss of Treg function and the development of anti-fetal CD8+ T cells. Figure created using BioRender.

Figure 2

Common features of vertically transmitted pathogens. Despite the many apparent differences between Listeria monocytogenes and Treponema pallidum, a careful comparison of the organisms reveals some common features which contribute to their ability to invade and cross the placenta. Figure created using BioRender.