Targeting and crossing of the human maternofetal barrier by Listeria monocytogenes: role of internalin interaction with trophoblast E-cadherin.
Listeria monocytogenes produces severe fetoplacental infections in humans. How it targets and crosses the maternofetal barrier is unknown. We used immunohistochemistry to examine the location of L. monocytogenes in placental and amniotic tissue samples obtained from women with fetoplacental listeriosis. The results raised the possibility that L. monocytogenes crosses the maternofetal barrier through the villous syncytiotrophoblast, with secondary infection occurring via the amniotic epithelium. Because epidemiological studies indicate that the bacterial surface protein, internalin (InlA), may play a role in human fetoplacental listeriosis, we investigated the cellular patterns of expression of its host receptor, E-cadherin, at the maternofetal interface. E-cadherin was found on the basal and apical plasma membranes of syncytiotrophoblasts and in villous cytotrophoblasts. Established trophoblastic cell lines, primary trophoblast cultures, and placental villous explants were each exposed to isogenic InlA+ or InlA- strains of L. monocytogenes, and to L. innocua expressing or not InlA. Quantitative assays of cellular invasion demonstrated that bacterial entry into syncytiotrophoblasts occurs via the apical membrane in an InlA-E-cadherin dependent manner. In human placental villous explants, bacterial invasion of the syncytiotrophoblast barrier and underlying villous tissue and subsequent replication produces histopathological lesions that mimic those seen in placentas of women with listeriosis. Thus, the InlA-E-cadherin interaction that plays a key role in the crossing of the intestinal barrier in humans is also exploited by L. monocytogenes to target and cross the placental barrier. Such a ligand-receptor interaction allowing a pathogen to specifically cross the placental villous trophoblast barrier has not been reported previously.
Lecuit
Marc
M
Unité des Interactions Bactéries-Cellules and Unité d'Histotechnologie et Pathologie, Institut Pasteur, Paris 75015, France. mlecuit@pasteur.fr
Nelson
D Michael
DM
Smith
Steve D
SD
Khun
Huot
H
Huerre
Michel
M
Vacher-Lavenu
Marie-Cécile
MC
Gordon
Jeffrey I
JI
Cossart
Pascale
P
D001426:Bacterial Proteins / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008089:Listeria monocytogenes / Q000502:physiology*; D008088:Listeriosis / Q000635:transmission*; D008431:Maternal-Fetal Exchange; D010920:Placenta / Q000378:metabolism / Q000382:microbiology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D011485:Protein Binding; D014327:Trophoblasts / Q000378:metabolism*
D001426:Bacterial Proteins; D015820:Cadherins; C103178:inlC protein, Listeria monocytogenes