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Jeschke, U.

Publications and source records attributed to Jeschke, U..

2 recordsLinked to original sources

Neutrophils are critical for placental and fetal infection with the human pathogen Listeria monocytogenes

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 SummaryMaternal circulating neutrophils act as survival niche for Listeria monocytogenes and facilitate placental/fetal infection with Listeria during pregnancy.

immunology↗

The transcription factor RIP140 regulates interferon γ signaling in breast cancer

RIP140 (receptor interacting protein of 140 kDa) is an important player in breast cancer (BC) by regulating key cellular pathways such as nuclear hormone receptors signaling. In order to identify additional genes specifically regulated by RIP140 in BC, we performed an RNA sequencing after silencing its expression in MCF-7 cells. We identified the interferon {gamma} (IFN{gamma}) signaling as being substantially repressed by RIP140 knock-down. Using the GBP1 (guanylate binding protein 1) gene as a reporter of IFN{gamma} signaling, we demonstrated its robust induction by RIP140 through an ISRE motif, leading to a significant reduction of its induction upon IFN{gamma} treatment. Furthermore, we showed that low levels of RIP140 amplified the IFN{gamma}-dependent inhibition of BC cell proliferation. In line with these data, reanalysis of transcriptomic data obtained in human BC samples, revealed that IFN{gamma} levels were associated with good prognosis only for BC patients exhibiting tumors expressing low levels of RIP140, thus confirming its effect on the anti-tumor activity of IFN{gamma} provided by our experimental data. Altogether, this study identifies RIP140 as a new regulator of IFN{gamma} signaling in breast tumorigenesis.

cancer biology↗