Crosstalk Between Trophoblast and Macrophage at the Maternal-Fetal Interface: Current Status and Future Perspectives

Ding, Jinli; Zhang, Yan; Cai, Xiaopeng; Diao, Lianghui; Yang, Chaogang; Yang, Jing

doi:10.3389/fimmu.2021.758281

Cited by 40 publications

(34 citation statements)

References 104 publications

(149 reference statements)

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“…71,72 Ultimately, trophoblasts and macrophages form an extensive communication network at the maternal-fetal interface and help maintain key physiological functions associated with gestation. 73 Maternal blood circulation through the placenta is established by the end of the first trimester providing a mechanism for immune activation in maternal circulation, especially monocytes. 74 The fundamental zones of the placenta begin to develop including villous trees that connect embryonic and maternal circulatory systems.…”

Section: The Immune L Andsc Ape At the Maternal-fe Tal Interfacementioning

confidence: 99%

“…In vitro models have shown that human trophoblasts promote the differentiation of peripheral CD14 + monocytes into CD14 + CD206 high CD86 low macrophages that have a unique transcriptional profile in response to TLR4 activation, characterized by the expression of type 1 interferons 71,72 . Ultimately, trophoblasts and macrophages form an extensive communication network at the maternal‐fetal interface and help maintain key physiological functions associated with gestation 73 …”

Section: The Immune Landscape At the Maternal‐fetal Interfacementioning

confidence: 99%

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Monocytes and macrophages in pregnancy: The good, the bad, and the ugly*

True

Blanton

Sureshchandra

et al. 2022

Immunological Reviews

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A successful human pregnancy requires precisely timed adaptations by the maternal immune system to support fetal growth while simultaneously protecting mother and fetus against microbial challenges. The first trimester of pregnancy is characterized by a robust increase in innate immune activity that promotes successful implantation of the blastocyst and placental development. Moreover, early pregnancy is also a state of increased vulnerability to vertically transmitted pathogens notably, human immunodeficiency virus (HIV), Zika virus (ZIKV), SARS‐CoV‐2, and Listeria monocytogenes. As gestation progresses, the second trimester is marked by the establishment of an immunosuppressive environment that promotes fetal tolerance and growth while preventing preterm birth, spontaneous abortion, and other gestational complications. Finally, the period leading up to labor and parturition is characterized by the reinstatement of an inflammatory milieu triggering childbirth. These dynamic waves of carefully orchestrated changes have been dubbed the “immune clock of pregnancy.” Monocytes in maternal circulation and tissue‐resident macrophages at the maternal‐fetal interface play a critical role in this delicate balance. This review will summarize the current data describing the longitudinal changes in the phenotype and function of monocyte and macrophage populations in healthy and complicated pregnancies.

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Section: The Immune L Andsc Ape At the Maternal-fe Tal Interfacementioning

confidence: 99%

Section: The Immune Landscape At the Maternal‐fetal Interfacementioning

confidence: 99%

Monocytes and macrophages in pregnancy: The good, the bad, and the ugly*

True

Blanton

Sureshchandra

et al. 2022

Immunological Reviews

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“…A large number of studies have indicated that M1 macrophages affect the microenvironment of the maternal-fetal interface via secretion of cytokines [ 28 , 29 ]. To investigate the mechanism of regulation of cell function of trophoblasts by M1 macrophages that had been polarized by EV miR-196a-5p, we performed qPCR and ELISA to analyze the levels of iNOS, IL-1 β , and TNF- α in the cell lysates and CM of PMA-pretreated THP-1 cells.…”

Section: Resultsmentioning

confidence: 99%

“…The ratio of M1 macrophages in the decidual tissue of unexplained RM patients was significantly increased compared with individuals who had a healthy pregnancy in the first trimester [ 14 ]. It has been reported that M1 macrophages play important roles in regulating trophoblast function via secretion of cytokines [ 28 ]. It has been reported that TNF inhibitors could reduce the immune rejection rate and improve the pregnancy outcomes in females suffering from RM [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

miR-196a-5p-Rich Extracellular Vesicles from Trophoblasts Induce M1 Polarization of Macrophages in Recurrent Miscarriage

Zhang

Tao

Cai

et al. 2022

Journal of Immunology Research

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Purpose. Numerous studies have described the presence of crosstalk between trophoblasts and macrophages and the critical role it plays in recurrent miscarriage (RM). However, the mechanism of trophoblast-derived extracellular vesicle (EV) miRNAs and their interactions with decidual macrophages in the pathogenesis of RM remains unclear. Materials and Methods. miRNA-seq was used to identify the differentially expressed miRNAs between RM patients and healthy controls. qPCR and in situ hybridization assays were performed to analyze the expression levels of miR-196a-5p in RM. THP-1 cells were treated with EVs, and qPCR and flow cytometry were performed to explore the polarization of macrophages. To explore the crosstalk between trophoblasts and macrophages, a coculture model and a series of cell function assays were performed. Results. We first demonstrated that miR-196a-5p expression was higher in the cytotrophoblasts of villous tissues and plasma EVs from RM patients. miR-196a-5p derived from trophoblasts could be transferred into macrophages via EVs to induce M1 polarization via IκBα-mediated NF-κB pathway. Moreover, we found that M1 macrophages induced by EV miR-196a-5p derived from trophoblasts conversely regulated the proliferation, migration, and apoptosis of trophoblasts via TNF-α. Conclusions. This study indicated that trophoblast-derived EV miR-196a-5p was positively associated with RM and functioned by regulating the crosstalk between trophoblasts and macrophages. These findings may attribute to identify a novel biomarker specific for RM.

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“…HCMV spreads systemically and placental infection is likely initiated via infected maternal blood myeloid cells [50]. Within the placenta, trophoblast invasion, migration and fusion are highly coordinated events that are regulated by macrophage interactions [51]. Studies of placentas taken from congenital infections demonstrate that HCMV markedly perturbs the signaling repertoire responsible for normal trophoblast function, correlating with their aberrant proliferation, migration, and invasion [27].…”

Section: Discussionmentioning

confidence: 99%

Constitutive Signaling by the Human Cytomegalovirus G Protein Coupled Receptor Homologs US28 and UL33 Enables Trophoblast Migration In Vitro

Davis-Poynter

Farrell

2022

Viruses

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Human cytomegalovirus (HCMV) encodes four homologs of G protein coupled receptors (vGPCRs), of which two, designated UL33 and US28, signal constitutively. UL33 and US28 are also conserved with chemokine receptors: US28 binds numerous chemokine classes, including the membrane bound chemokine, fractalkine; whereas UL33 remains an orphan receptor. There is emerging data that UL33 and US28 each contribute to HCMV associated disease, although no studies to date have reported their potential contribution to aberrant placental physiology that has been detected with HCMV congenital infection. We investigated the signaling repertoire of UL33 and US28 and their potential to enable trophoblast mobilization in vitro. Results demonstrate the constitutive activation of CREB by each vGPCR in ACIM-88 and HTR-8SVneo trophoblasts; constitutive NF-kB activation was detected for US28 only. Constitutive signaling by each vGPCR enabled trophoblast migration. For US28, fractalkine exhibited inverse agonist activity and dampened trophoblast migration. UL33 stimulated expression of both p38 mitogen activated (MAP) and Jun N-terminal (JNK) kinases; while p38 MAP kinase stimulated CREB, JNK was inhibitory, suggesting that UL33 dependent CREB activation was regulated by p38/JNK crosstalk. Given that chemokines and their receptors are important for placental development, these data point to the potential of HCMV UL33 and US28 to interfere with trophoblast responses which are important for normal placental development.

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Crosstalk Between Trophoblast and Macrophage at the Maternal-Fetal Interface: Current Status and Future Perspectives

Cited by 40 publications

References 104 publications

Monocytes and macrophages in pregnancy: The good, the bad, and the ugly*

Monocytes and macrophages in pregnancy: The good, the bad, and the ugly*

miR-196a-5p-Rich Extracellular Vesicles from Trophoblasts Induce M1 Polarization of Macrophages in Recurrent Miscarriage

Constitutive Signaling by the Human Cytomegalovirus G Protein Coupled Receptor Homologs US28 and UL33 Enables Trophoblast Migration In Vitro

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