Maternal B Cell-Intrinsic MyD88 Signaling Mediates LPS-Driven Intrauterine Fetal Death
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...
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MDPI AG
2021-10-01
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| author | Mandy Busse Susanne Plenagl Norina Kim Jutta Campe Andreas J. Müller Kerry Tedford Anne Schumacher Ana Claudia Zenclussen |
| author_facet | Mandy Busse Susanne Plenagl Norina Kim Jutta Campe Andreas J. Müller Kerry Tedford Anne Schumacher Ana Claudia Zenclussen |
| author_sort | Mandy Busse |
| collection | DOAJ |
| description | 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<sup>-/-</sup>) mice. B cells isolated from wild-type (WT), BMyD88<sup>-/-</sup>, CD19<sup>-/-</sup> and MyD88<sup>-/-</sup> dams on gestational day (gd) 10 responded differently to LPS concerning cytokine secretion. In vivo LPS challenge on gd 10 provoked IUFD in CD19<sup>-/-</sup> mothers with functional MyD88, while fetuses from BMyD88<sup>-/-</sup> and MyD88<sup>-/-</sup> mice were protected. These outcomes were associated with altered cytokine levels in the maternal serum and changes in CD4<sup>+</sup> 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. |
| first_indexed | 2024-03-10T06:39:56Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:39:56Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-d6f0fca18e154bb68fad5c319115a7712023-11-22T17:47:39ZengMDPI AGCells2073-44092021-10-011010269310.3390/cells10102693Maternal B Cell-Intrinsic MyD88 Signaling Mediates LPS-Driven Intrauterine Fetal DeathMandy Busse0Susanne Plenagl1Norina Kim Jutta Campe2Andreas J. Müller3Kerry Tedford4Anne Schumacher5Ana Claudia Zenclussen6Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, 39108 Magdeburg, GermanyExperimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, 39108 Magdeburg, GermanyExperimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, 39108 Magdeburg, GermanyInstitute for Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, GermanyInstitute of Biochemistry and Cell Biology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, GermanyDepartment of Environmental Immunology, Helmholtz Centre for Environmental Research-UFZ, 04318 Leipzig, GermanyDepartment of Environmental Immunology, Helmholtz Centre for Environmental Research-UFZ, 04318 Leipzig, GermanyImmunological 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<sup>-/-</sup>) mice. B cells isolated from wild-type (WT), BMyD88<sup>-/-</sup>, CD19<sup>-/-</sup> and MyD88<sup>-/-</sup> dams on gestational day (gd) 10 responded differently to LPS concerning cytokine secretion. In vivo LPS challenge on gd 10 provoked IUFD in CD19<sup>-/-</sup> mothers with functional MyD88, while fetuses from BMyD88<sup>-/-</sup> and MyD88<sup>-/-</sup> mice were protected. These outcomes were associated with altered cytokine levels in the maternal serum and changes in CD4<sup>+</sup> 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.https://www.mdpi.com/2073-4409/10/10/2693intrauterine fetal deathpregnancyinflammationB cells |
| spellingShingle | Mandy Busse Susanne Plenagl Norina Kim Jutta Campe Andreas J. Müller Kerry Tedford Anne Schumacher Ana Claudia Zenclussen Maternal B Cell-Intrinsic MyD88 Signaling Mediates LPS-Driven Intrauterine Fetal Death Cells intrauterine fetal death pregnancy inflammation B cells |
| title | Maternal B Cell-Intrinsic MyD88 Signaling Mediates LPS-Driven Intrauterine Fetal Death |
| title_full | Maternal B Cell-Intrinsic MyD88 Signaling Mediates LPS-Driven Intrauterine Fetal Death |
| title_fullStr | Maternal B Cell-Intrinsic MyD88 Signaling Mediates LPS-Driven Intrauterine Fetal Death |
| title_full_unstemmed | Maternal B Cell-Intrinsic MyD88 Signaling Mediates LPS-Driven Intrauterine Fetal Death |
| title_short | Maternal B Cell-Intrinsic MyD88 Signaling Mediates LPS-Driven Intrauterine Fetal Death |
| title_sort | maternal b cell intrinsic myd88 signaling mediates lps driven intrauterine fetal death |
| topic | intrauterine fetal death pregnancy inflammation B cells |
| url | https://www.mdpi.com/2073-4409/10/10/2693 |
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