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Title (Primary) Maternal B cell-intrinsic MyD88 signaling mediates LPS-driven intrauterine fetal death
Author Busse, M.; Plenagl, S.; Campe, N.K.J.; Müller, A.J.; Tedford, K.; Schumacher, A.; Zenclussen, A.C.;
Journal Cells
Year 2021
Department IMMU;
Volume 10
Issue 10
Language englisch;
Keywords intrauterine fetal death; pregnancy; inflammation; B cells
Abstract Immunological networks balance tolerance towards paternal alloantigens during pregnancy with normal immune response to pathogens. Subclinical infections can impact this balance and lead to preterm birth or even intrauterine fetal death (IUFD). We recently showed that loss of maternal B cells renders murine fetuses susceptible to IUFD after LPS exposure. Since the signaling pathway involved in this B-cell mediated response remains unclear, we aimed to understand the participation of MyD88 in this response using B-cell-specific MyD88-deficient (BMyD88-/-) mice. B cells isolated from wild-type (WT), BMyD88-/-, CD19-/- and MyD88-/- dams on gestational day (gd) 10 responded differently to LPS concerning cytokine secretion. In vivo LPS challenge on gd 10 provoked IUFD in CD19-/- mothers with functional MyD88, while fetuses from BMyD88-/- and MyD88-/- mice were protected. These outcomes were associated with altered cytokine levels in the maternal serum and changes in CD4+ T-cell responses. Overall, the loss of MyD88 signaling in maternal B cells prevents the activation of cytokine release that leads to IUFD. Thus, while MyD88 signaling in maternal B cells protects the mother from infection, it ultimately kills the fetus. Understanding the cellular mechanisms underlying infection-driven pregnancy complications is the first step to designing powerful therapeutic strategies in the future.
ID 25206
Persistent UFZ Identifier https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=25206
Busse, M., Plenagl, S., Campe, N.K.J., Müller, A.J., Tedford, K., Schumacher, A., Zenclussen, A.C. (2021):
Maternal B cell-intrinsic MyD88 signaling mediates LPS-driven intrauterine fetal death
Cells 10 (10), art. 2693