Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis

Abstract

The bacterial pathogen Listeria monocytogenes causes foodborne systemic disease in pregnant women, which can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to the placenta and fetus. Host-pathogen interactions in the decidua during this early stage of infection remain poorly understood. Here, we assessed the dynamics of L. monocytogenes infection in primary human decidual organ cultures and in the murine decidua in vivo. A high inoculum was necessary to infect both human and mouse deciduas, and the data support the existence of a barrier to initial colonization of the murine decidua. If successful, however, colonization in both species was followed by significant bacterial expansion associated with an inability of the decidua to mount appropriate innate cellular immune responses. The innate immune deficits included the failure of bacterial foci to attract macrophages and NK cells, cell types known to be important for early defenses against L. monocytogenes in the spleen, as well as a decrease in the tissue density of inflammatory Ly6C hi monocytes in vivo. These results suggest that the infectivity of the decidua is not the result of an enhanced recruitment of L. monocytogenes to the gestational uterus but rather is due to compromised local innate cellular immune responses.KEYWORDS Listeria monocytogenes, decidua, placenta T he pregnant uterus is a dynamic organ that supports fetoplacental growth, with many trophic functions provided by the decidua, the specialized endometrial tissue that encases the conceptus (1). The decidua also provides a unique immunological environment that blocks the maternal immune system from recognizing the conceptus as a foreign tissue and rejecting it as if it were a solid-organ transplant (2). As a consequence, this environment would be expected to provide opportunities for pathogens to infect the maternal-fetal interface. Indeed, infection of the decidua is now considered to be a critical first step in the hematogenous transmission of a variety of pathogens from mother to fetus (3-7). One such organism is the facultative, intracellular, Gram-positive bacterium Listeria monocytogenes, a clinically relevant foodborne pathogen that can cause severe disease in pregnant women. Once L. monocytogenes reaches the placenta, there are increased risks of severe maternal disease and pregnancy complications, including preterm labor and devastating fetal/neonatal morbidity and mortality (8, 9).Because of its experimental tractability, L. monocytogenes is an excellent model

Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface

“…Studies of tissue explants and histopathologic analysis of the placenta suggest that the decidua and chorionic villi have differing roles in the pathogenesis of relevant infections. The decidua may be a primary site of replication for several microorganisms associated with congenital disease, including cytomegalovirus (CMV) (McDonagh et al, 2006; Pereira et al, 2003; Weisblum et al, 2011), Zika virus (ZIKV) (Guzeloglu-Kayisli et al, 2020; Platt et al, 2018; Weisblum et al, 2017), and Listeria monocytogenes (Rizzuto et al, 2017), suggesting it may serve as a reservoir for these infections. By contrast, the placenta is largely resistant to infections and possesses a number of intrinsic mechanisms of innate defense.…”

Regulation of Th17 cells by P. UF1 against systemic Listeria monocytogenes infection

“…1 Listeria monocytogenes (L. m) is a Gram-positive intracellular bacterium that can be transmitted via contaminated food potentially resulting in sepsis and even death. Additionally, this foodborne pathogen also causes systemic diseases, particularly in pregnant women potentially leading to preterm labor, stillbirth, and severe neonatal inflammatory diseases 2 . Furthermore, L. m outbreaks recently have been particularly deadly; thus, gaining insights from the protective immune mechanisms implicated in the clearance of this pathogen requires further investigation, which may result in developing new therapies against this pathogen.…”

Streptococcus pyogenes infects human endometrium by limiting its immune response

“…Pathogens able to infect maternal-fetal interface are limited (63). Listeria monocytogenes causes foodborne disease with 12-20 times more prevalence in pregnant women, yet human decidua is a barrier to initial infection, inferring decidual stromal cells per se have defense mechanisms against L. monocytogenes (64). GBS is more prevalent in female reproductive tract than GAS but typically causes less severe maternal infection.…”