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Frontiers in Immunology 2020During pregnancy, the placenta forms the anatomical barrier between the mother and developing fetus. Infectious agents can potentially breach the placental barrier... (Review)
Review
During pregnancy, the placenta forms the anatomical barrier between the mother and developing fetus. Infectious agents can potentially breach the placental barrier resulting in pathogenic transmission from mother to fetus. Innate immune responses, orchestrated by maternal and fetal cells at the decidual-placental interface, are the first line of defense to avoid vertical transmission. Here, we outline the anatomy of the human placenta and uterine lining, the decidua, and discuss the potential capacity of pathogen pattern recognition and other host defense strategies present in the innate immune cells at the placental-decidual interface. We consider major congenital infections that access the placenta from hematogenous or decidual route. Finally, we highlight the challenges in studying human placental responses to pathogens and vertical transmission using current experimental models and identify gaps in knowledge that need to be addressed. We further propose novel experimental strategies to address such limitations.
Topics: Animals; Decidua; Disease Models, Animal; Female; Humans; Immunity, Innate; Infections; Infectious Disease Transmission, Vertical; Placenta; Pregnancy
PubMed: 33013876
DOI: 10.3389/fimmu.2020.02070 -
American Journal of Reproductive... Dec 2021Mucosal-Associated Invariant T (MAIT) cells have been recently identified at the maternal-fetal interface. However, transcriptional programming of decidual MAIT cells in...
PROBLEM
Mucosal-Associated Invariant T (MAIT) cells have been recently identified at the maternal-fetal interface. However, transcriptional programming of decidual MAIT cells in pregnancy remains poorly understood.
METHOD OF STUDY
We employed a multiomic approach to address this question. Mononuclear cells from the decidua basalis and parietalis, and control PBMCs, were analyzed via flow cytometry to investigate MAIT cells in the decidua and assess their transcription factor expression. In a separate study, both decidual and matched peripheral MAIT cells were analyzed using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) coupled with gene expression analysis. Lastly, decidual MAIT cells were stimulated with E.coli and expression of MR1 by antigen presenting cells was measured to evaluate decidual MAIT cell function.
RESULTS
First, we identified MAIT cells in both the decidua basalis and parietalis. CITE-seq, coupled with scRNA-seq gene expression analysis, highlighted transcriptional programming differences between decidual and matched peripheral MAIT cells at a single cell resolution. Transcription factor expression analysis further highlighted transcriptional differences between decidual MAIT cells and non-matched peripheral MAIT cells. Functionally, MAIT cells are skewed towards IFNγ and TNFα production upon stimulation, with E.coli leading to IFNγ production. Lastly, we demonstrate that MR1, the antigen presenting molecule restricting MAIT cells, is expressed by decidual APCs.
CONCLUSION
MAIT cells are present in the decidua basalis and obtain a unique gene expression profile. The presence of MR1 on APCs coupled with in vitro activation by E.coli suggests that MAIT cells might be involved in tissue-repair mechanisms at the maternal-fetal interface.
Topics: Decidua; Female; Flow Cytometry; Humans; Leukocytes; Mucosal-Associated Invariant T Cells; Placenta; Pregnancy
PubMed: 34411378
DOI: 10.1111/aji.13495 -
Frontiers in Immunology 2018Innate lymphoid cells (ILC) are developmentally related cell subsets that play a major role in innate defenses against pathogens, in lymphoid organogenesis and in tissue... (Review)
Review
Innate lymphoid cells (ILC) are developmentally related cell subsets that play a major role in innate defenses against pathogens, in lymphoid organogenesis and in tissue remodeling. The best characterized ILC are natural killer (NK) cells. They are detectable in decidua in the early phases of pregnancy. During the first trimester, NK cells represent up to 50% of decidua lymphocytes. Differently from peripheral blood (PB) NK cells, decidual NK (dNK) cells are poorly cytolytic, and, instead of IFNγ, they release cytokines/chemokines that induce neo-angiogenesis, tissue remodeling, and placentation. dNK interact with resident myeloid cells and participate in the induction of regulatory T cells that play a pivotal role in maintaining an efficient fetal-maternal tolerance. dNK cells may originate from CD34 precursor cells present and/or from immature NK cells already present in endometrial tissue and/or from PB NK cells migrated to decidua. In addition to NK cells, also ILC3 are present in human decidua during the first trimester. Decidual ILC3 include both natural cytotoxic receptor (NCR) and NCR cells, producing respectively IL-8/IL-22/GM-CSF and TNF/IL-17. NCRILC3 have been shown to establish physical and functional interactions with neutrophils that, in turn, produce factors that are crucial for pregnancy induction/maintenance and for promoting the early inflammatory phase, a fundamental process for a successful pregnancy. While NCRILC3 display a stable phenotype, most of NCRILC3 may acquire phenotypic and functional features of NCRILC3. In conclusion, both NK cells and ILC3 are present in human decidua and may establish functional interactions with immune and myeloid cells playing an important role both in innate defenses and in tissue building/remodeling/placentation during the early pregnancy. It is conceivable that altered numbers or function of these cells may play a role in pregnancy failure.
Topics: Cell Communication; Cellular Microenvironment; Decidua; Disease Susceptibility; Female; Humans; Immune Tolerance; Immunity, Innate; Killer Cells, Natural; Lymphocyte Subsets; Neutrophils; Pregnancy; Stromal Cells
PubMed: 30154799
DOI: 10.3389/fimmu.2018.01897 -
Journal of Reproductive Immunology Nov 2017The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus, despite being recognized by the maternal immune cells.... (Review)
Review
The maternal-fetal interface undergoes dynamic changes to allow the fetus to grow and develop in the uterus, despite being recognized by the maternal immune cells. Within the innate immune system, decidual natural killer cells and antigen presenting cells (including macrophages and dendritic cells) that comprise a large proportion of the decidual leukocyte populations play an important role in modulating trophoblast invasion, angiogenesis and vascular remodeling. On the other hand, within the adaptive immune system, CD8 T cells, effector CD4 T cells, Foxp3 regulatory T cells and CD4HLA-G suppressor T cells are identified as potential players in maintaining immune tolerance toward the semi-allogeneic fetus. This review discusses how these key immune cells contribute to pregnancy outcome and the complex interactions between the innate and adaptive immune system during human pregnancy.
Topics: Adaptive Immunity; Animals; Antigen-Presenting Cells; Decidua; Female; Forkhead Transcription Factors; Homeostasis; Humans; Immune Tolerance; Immunity, Innate; Killer Cells, Natural; Placental Circulation; Pregnancy; T-Lymphocytes, Regulatory
PubMed: 29055791
DOI: 10.1016/j.jri.2017.10.045 -
Roumanian Archives of Microbiology and... 2015The mammalian conceptus is a semi-allograft. The maternal tolerance towards semi-allograft is primed by a battery of cytokines and resident decidual cells. Invasion of... (Review)
Review
The mammalian conceptus is a semi-allograft. The maternal tolerance towards semi-allograft is primed by a battery of cytokines and resident decidual cells. Invasion of embryonic trophoblast, decidual vascular remodeling and unresponsive incipient 'Triple-negative' (CD3-, CD4- and CD8-) T-cells of foetus promote normal pregnancy. On the other hand, the maternal cytokine profile shift towards Th1 response is shown to enhance the risk during pregnancy. The periodical examination of maternal serum levels of Th1 and Th2 response mediated cytokines constitutes prognostic biomarkers to initiate therapeutic regimens.
Topics: Animals; Cytokines; Decidua; Female; Humans; Pregnancy; Trophoblasts
PubMed: 27328524
DOI: No ID Found -
Cell and Tissue Research Jan 2016The maternal-fetal interface undergoes dynamic changes that promote successful development of the embryo/fetal allograft during pregnancy. This immune privilege of the... (Review)
Review
The maternal-fetal interface undergoes dynamic changes that promote successful development of the embryo/fetal allograft during pregnancy. This immune privilege of the conceptus is mediated through local and systemic cellular responses. In species in which endometrial decidualization accompanies pregnancy, unique immune cell niches are found. Many studies have addressed the enigmatic roles of uterine (u)NK cells as killers and helpers because they are frequently found in the uterine lining and decidua of normal and pathological pregnancies. Accumulating evidence indicates that uNK cells are induced and transformed by sensing signals within their microenvironment to both protect the mother from the fetal allograft and support the fetus during its development. Here, we review the mechanisms that modulate these functions of uNK cells during pregnancy. We suggest that uNK cells must be tightly regulated in order to serve these two roles and support a healthy pregnancy.
Topics: ADAM Proteins; Animals; Cytokines; Decidua; Embryo Implantation; Female; Humans; Immunity, Innate; Killer Cells, Natural; Major Histocompatibility Complex; Neovascularization, Physiologic; Placentation; Pregnancy; Receptors, KIR; T-Lymphocytes, Regulatory; Trophoblasts
PubMed: 26572540
DOI: 10.1007/s00441-015-2315-4 -
The International Journal of... 2020The eutherian species evolved an elaborate uterus to allow viviparity. For successful pregnancy, the uterus must not only be differentiated, but must also function... (Review)
Review
The eutherian species evolved an elaborate uterus to allow viviparity. For successful pregnancy, the uterus must not only be differentiated, but must also function optimally and any defects in uterus differentiation and/or function can lead to infertility. The homoebox gene HOXA10 has emerged to be a key player in both uterine development and its optimal functioning in adulthood. Within the Abd-B family, the posterior Hoxa genes play a dominant role in anterio-posterior segmentation of the Müllerian ducts in mammals, with Hoxa10 having a central role in uterine segmentation. In the adult endometrium, HOXA10 is expressed by endometrial cells and is regulated in a cyclic manner under the influence of ovarian steroids. During embryo implantation, expression of HOXA10 is increased in endometrial stromal cells by signals from the embryo to govern stromal cell transformation to decidual cells. Once decidualization is initiated, HOXA10 is rapidly downregulated to activate expression of pro-invasive factors to promote trophoblast invasion. We propose that HOXA10 governs embryo implantation in a three-step process: 1) acquisition of endometrial receptivity, 2) responding to signals from the blastocyst to modify receptive endometrium for decidualization 3) making the decidua conductive for trophoblast invasion and placentation. There is currently ample evidence that expression of HOXA10 is deregulated in a variety of "endometriopathies" such as endometriosis and endometrial cancers. Overall, HOXA10 appears to be the master regulator of endometrial health and a central determinant of fertility in mammals.
Topics: Animals; Cell Differentiation; Decidua; Embryo Implantation; Endometrium; Female; Gene Expression Regulation, Developmental; Homeobox A10 Proteins; Humans; Placentation; Pregnancy
PubMed: 32659011
DOI: 10.1387/ijdb.190120dm -
Immunology Letters Dec 2015Both experimental and clinical studies revealed that stromal cells (SC) are present in decidua (DSC) and placenta (PSC) at the early and late phase of pregnancy,... (Review)
Review
Both experimental and clinical studies revealed that stromal cells (SC) are present in decidua (DSC) and placenta (PSC) at the early and late phase of pregnancy, respectively, and they may contribute to the induction of an anti-inflammatory/tolerogenic microenvironment crucial for the establishment/maintenance of successful pregnancy. These cells share common features with mesenchymal SC. In the present contribution, we provide an overall view on DSC features and on their ability to recruit NK cells and to regulate both differentiation and function not only of NK cells but also of CD14(+) myeloid cells. NK cells represent the large majority of leukocytes populating decidual tissues during the first trimester of pregnancy. Their cross-talk with DSC is thought to play a key role in the establishment of feto-maternal tolerance. We also discuss recent data suggesting that DSC may contribute to tissue remodeling, placentation, and recruitment of leukocytes also through their interaction with innate lymphoid cells (ILC) such as ILC3, that have recently been shown to be present in decidual tissue.
Topics: Cell Communication; Decidua; Female; Humans; Immune System; Mesenchymal Stem Cells; Models, Immunological; Placenta; Pregnancy; Stromal Cells
PubMed: 25986011
DOI: 10.1016/j.imlet.2015.05.006 -
Journal of Leukocyte Biology Oct 2016
Topics: Decidua; Humans; Killer Cells, Natural; Uterus
PubMed: 27697917
DOI: 10.1189/jlb.1CE0316-162R -
Biomolecules May 2021Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising... (Review)
Review
Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising poor placentation associated with the failure of fertilized egg implantation. Successful implantation and placentation require maternal immunotolerance of the fertilized egg as a semi-allograft and appropriate extravillous trophoblast (EVT) invasion of the decidua and myometrium. The disturbance of EVT invasion during implantation in PE results in impaired spiral artery remodeling. PE is thought to be caused by hypoxia during remodeling failure-derived poor placentation, which results in chronic inflammation. High-mobility group protein A (HMGA) is involved in the growth and invasion of cancer cells and likely in the growth and invasion of trophoblasts. Its mechanism of action is associated with immunotolerance. Thus, HMGA is thought to play a pivotal role in successful pregnancy, and its dysfunction may be related to the pathogenesis of PE. The evaluation of HMGA function and its changes in PE might confirm that it is a reliable biomarker of PE and provide prospects for PE treatment through the induction of EVT proliferation and invasion during the implantation.
Topics: Animals; Cell Proliferation; Decidua; Female; HMGA1a Protein; Humans; Pre-Eclampsia; Pregnancy; Trophoblasts
PubMed: 34072941
DOI: 10.3390/biom11060822