Myriam Ripphahn, Nikita Raj, Hellen Ishikawa-Ankerhold, Zhouyi Rong, Bastian Popper, Bianca Portugal Tavares de Moraes, Xia Li, Ying Chen, Roland Immler, Lou-Martha Wackerbarth, Dominic van den Heuvel, Barbara Schmidinger, Rainer Haas, Udo Jeschke, Sven Kehl, Anne Loesslein, Steffen Massberg, Farida Hellal, Ali Ertürk, Markus Sperandio
Abstract
Fetal listeriosis, caused by Listeria monocytogenes (Lm), represents a severe infectious disease. During pregnancy, the unique intrauterine environment permits Lm to breach the maternal-fetal barrier by infiltrating the placental trophoblast layer and ultimately leading to significant fetal morbidity and mortality. However, the exact pathways remain incompletely understood. In this study, we sought to elucidate the molecular mechanisms underlying the early stages of placental and fetal Lm infection. Our results reveal that neutrophils serve as a survival niche for Lm within the vasculature, facilitating placental and fetal infection in the mouse in vivo. This finding was further substantiated by in vitro studies using TLR2-stimulated trophoblast cells and Lm-infected neutrophils. Additionally, tissue-clearing analysis of Lm-infected placentas demonstrated neutrophil colocalization with Lm is rare within placental tissue. Collectively, our findings identify maternal neutrophils as an essential viability niche for Lm enabling their entry into trophoblast cells, thereby promoting placental and fetal infection.
One Sentence Summary Maternal circulating neutrophils act as survival niche for Listeria monocytogenes and facilitate placental/fetal infection with Listeria during pregnancy.
