B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection
The maternal balance between B regulatory (Breg) cells and inflammatory B cells is of central importance for protection against preterm birth (PTB). However, the impact of B cell signaling in early maternal and fetal immune responses on inflammatory insults remains underinvestigated. To understand w...
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/22/16091 |
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| author | Gina Marie Uehre Svetlana Tchaikovski Atanas Ignatov Ana Claudia Zenclussen Mandy Busse |
| author_facet | Gina Marie Uehre Svetlana Tchaikovski Atanas Ignatov Ana Claudia Zenclussen Mandy Busse |
| author_sort | Gina Marie Uehre |
| collection | DOAJ |
| description | The maternal balance between B regulatory (Breg) cells and inflammatory B cells is of central importance for protection against preterm birth (PTB). However, the impact of B cell signaling in early maternal and fetal immune responses on inflammatory insults remains underinvestigated. To understand which role B cells and B-cell-specific signaling play in the pathogenesis of PTB, the later was induced by an injection of LPS in B cell-sufficient WT mice, CD19<sup>−/−</sup>, BMyD88<sup>−/−</sup> and µMT murine dams at gestational day 16 (gd 16). WT dams developed a strong inflammatory response in their peritoneal cavity (PC), with an increased infiltration of granulocytes and enhanced IL-6, TNF-α, IL-17 and MCP-1 levels. However, they demonstrated a reduced NOS2 expression of PC macrophages 4 h after the LPS injection. Simultaneously, LPS-challenged WT dams upregulated pregnancy-protective factors like IL-10 and TARC. The concentrations of inflammatory mediators in the placental supernatants, amniotic fluids, fetal serums and gestational tissues were lower in LPS-challenged WT dams compared to CD19<sup>−/−</sup>, BMyD88<sup>−/−</sup> and µMT dams, thereby protecting WT fetuses from being born preterm. B cell deficiency, or the loss of B-cell-specific CD19 or MyD88 expression, resulted in an early shift from immune regulation towards inflammation at the fetomaternal interface and fetuses, resulting in PTB. |
| first_indexed | 2024-03-09T16:47:28Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:47:28Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f654aad84cd642afb187ac47d98e34072023-11-24T14:45:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221609110.3390/ijms242216091B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal RejectionGina Marie Uehre0Svetlana Tchaikovski1Atanas Ignatov2Ana Claudia Zenclussen3Mandy Busse4Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, 39108 Magdeburg, GermanyUniversity Hospital for Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, 39108 Magdeburg, GermanyUniversity Hospital for Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, 39108 Magdeburg, GermanyDepartment of Environmental Immunology, Helmholtz Centre for Environmental Research-UFZ, 04318 Leipzig, GermanyExperimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, 39108 Magdeburg, GermanyThe maternal balance between B regulatory (Breg) cells and inflammatory B cells is of central importance for protection against preterm birth (PTB). However, the impact of B cell signaling in early maternal and fetal immune responses on inflammatory insults remains underinvestigated. To understand which role B cells and B-cell-specific signaling play in the pathogenesis of PTB, the later was induced by an injection of LPS in B cell-sufficient WT mice, CD19<sup>−/−</sup>, BMyD88<sup>−/−</sup> and µMT murine dams at gestational day 16 (gd 16). WT dams developed a strong inflammatory response in their peritoneal cavity (PC), with an increased infiltration of granulocytes and enhanced IL-6, TNF-α, IL-17 and MCP-1 levels. However, they demonstrated a reduced NOS2 expression of PC macrophages 4 h after the LPS injection. Simultaneously, LPS-challenged WT dams upregulated pregnancy-protective factors like IL-10 and TARC. The concentrations of inflammatory mediators in the placental supernatants, amniotic fluids, fetal serums and gestational tissues were lower in LPS-challenged WT dams compared to CD19<sup>−/−</sup>, BMyD88<sup>−/−</sup> and µMT dams, thereby protecting WT fetuses from being born preterm. B cell deficiency, or the loss of B-cell-specific CD19 or MyD88 expression, resulted in an early shift from immune regulation towards inflammation at the fetomaternal interface and fetuses, resulting in PTB.https://www.mdpi.com/1422-0067/24/22/16091preterm birthpregnancylipopolysaccharideinflammationB cells |
| spellingShingle | Gina Marie Uehre Svetlana Tchaikovski Atanas Ignatov Ana Claudia Zenclussen Mandy Busse B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection International Journal of Molecular Sciences preterm birth pregnancy lipopolysaccharide inflammation B cells |
| title | B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection |
| title_full | B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection |
| title_fullStr | B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection |
| title_full_unstemmed | B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection |
| title_short | B Cells Induce Early-Onset Maternal Inflammation to Protect against LPS-Induced Fetal Rejection |
| title_sort | b cells induce early onset maternal inflammation to protect against lps induced fetal rejection |
| topic | preterm birth pregnancy lipopolysaccharide inflammation B cells |
| url | https://www.mdpi.com/1422-0067/24/22/16091 |
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