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1.
J Immunol ; 207(10): 2433-2444, 2021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34663619

RESUMO

Throughout gestation, the maternal immune system is tightly modulated to allow growth of a semiallogeneic fetus. During the third trimester, the maternal immune system shifts to a proinflammatory phenotype in preparation for labor. What induces this shift remains unclear. Cell-free fetal DNA (cffDNA) is shed by the placenta and enters maternal circulation throughout pregnancy. Levels of cffDNA are increased as gestation progresses and peak before labor, coinciding with a shift to proinflammatory maternal immunity. Furthermore, cffDNA is abnormally elevated in plasma from women with complications of pregnancy, including preterm labor. Given the changes in maternal immunity at the end of pregnancy and the role of sterile inflammation in the pathophysiology of spontaneous preterm birth, we hypothesized that cffDNA can act as a damage-associated molecular pattern inducing an inflammatory cytokine response that promotes hallmarks of parturition. To test this hypothesis, we stimulated human maternal leukocytes with cffDNA from primary term cytotrophoblasts or maternal plasma and observed significant IL-1ß and CXCL10 secretion, which coincides with phosphorylation of IFN regulatory factor 3 and caspase-1 cleavage. We then show that human maternal monocytes are crucial for the immune response to cffDNA and can activate bystander T cells to secrete proinflammatory IFN-γ and granzyme B. Lastly, we find that the monocyte response to cffDNA leads to vascular endothelium activation, induction of myometrial contractility, and PGE2 release in vitro. Our results suggest that the immune response to cffDNA can promote key features of the parturition cascade, which has physiologic consequences relevant to the timing of labor.


Assuntos
Ácidos Nucleicos Livres/imunologia , Feto/imunologia , Monócitos/imunologia , Parto/imunologia , Trofoblastos/imunologia , Feminino , Humanos , Gravidez
2.
Front Immunol ; 12: 689181, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531852

RESUMO

Transforming growth factor-ß (TGF-ß) is composed of three isoforms, TGF-ß1, TGF-ß2, and TGF-ß3. TGF-ß1 is a cytokine with multiple biological functions that has been studied extensively. It plays an important role in regulating the differentiation of immune cells and maintaining immune cell functions and immune homeostasis. Pregnancy is a carefully regulated process. Controlled invasion of trophoblasts, precise coordination of immune cells and cytokines, and crosstalk between trophoblasts and immune cells play vital roles in the establishment and maintenance of normal pregnancy. In this systematic review, we summarize the role of TGF-ß1 in regulating fetal-maternal immune tolerance in healthy and pathological pregnancies. During healthy pregnancy, TGF-ß1 induces the production of regulatory T cells (Tregs), maintains the immunosuppressive function of Tregs, mediates the balance of M1/M2 macrophages, and regulates the function of NK cells, thus participating in maintaining fetal-maternal immune tolerance. In addition, some studies have shown that TGF-ß1 is dysregulated in patients with recurrent spontaneous abortion or preeclampsia. TGF-ß1 may play a role in the occurrence and development of these diseases and may be a potential target for the treatment of these diseases.


Assuntos
Tolerância Imunológica , Gravidez/imunologia , Fator de Crescimento Transformador beta1/imunologia , Animais , Feminino , Feto/imunologia , Humanos
3.
Nat Commun ; 12(1): 4706, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349112

RESUMO

During mammalian pregnancy, immune cells are vertically transferred from mother to fetus. The functional role of these maternal microchimeric cells (MMc) in the offspring is mostly unknown. Here we show a mouse model in which MMc numbers are either normal or low, which enables functional assessment of MMc. We report a functional role of MMc in promoting fetal immune development. MMc induces preferential differentiation of hematopoietic stem cells in fetal bone marrow towards monocytes within the myeloid compartment. Neonatal mice with higher numbers of MMc and monocytes show enhanced resilience against cytomegalovirus infection. Similarly, higher numbers of MMc in human cord blood are linked to a lower number of respiratory infections during the first year of life. Our data highlight the importance of MMc in promoting fetal immune development, potentially averting the threats caused by early life exposure to pathogens.


Assuntos
Quimerismo , Feto/imunologia , Imunidade Materno-Adquirida/imunologia , Infecções/imunologia , Animais , Medula Óssea/metabolismo , Epigenoma , Feminino , Sangue Fetal/citologia , Hematopoese , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Lactente , Camundongos , Monócitos/citologia , Gravidez , Linfócitos T/citologia
4.
Biochim Biophys Acta Mol Basis Dis ; 1867(12): 166248, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34461257

RESUMO

The COVID-19 pandemic has infected nearly 178 million people and claimed the lives of over 3.8 million in less than 15 months. This has prompted a flurry of research studies into the mechanisms and effects of SARS-CoV-2 viral infection in humans. However, studies examining the effects of COVID-19 in pregnant women, their placentae and their babies remain limited. Furthermore, reports of safety and efficacy of vaccines for SARS-CoV-2 in pregnancy are limited. This review concisely summarises the case studies and research on COVID-19 in pregnancy, to date. It also reviews the mechanism of infection with SARS-CoV-2, and its reliance and effects upon the renin-angiotensin-aldosterone system. Overall, the data suggest that infection during pregnancy can be dangerous at any time, but this risk to both the mother and fetus, as well as placental damage, increases during the third trimester. The possibility of vertical transmission, which is explored in this review, remains contentious. However, maternal infection with SARS-CoV-2 can increase risk of miscarriage, preterm birth and stillbirth, which is likely due to damage to the placenta.


Assuntos
COVID-19/metabolismo , Feto/imunologia , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Feminino , Feto/virologia , Humanos , Recém-Nascido , Pandemias , Placenta/metabolismo , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/prevenção & controle , SARS-CoV-2/isolamento & purificação
5.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360849

RESUMO

Gestational Diabetes Mellitus (GDM) is a transitory metabolic condition caused by dysregulation triggered by intolerance to carbohydrates, dysfunction of beta-pancreatic and endothelial cells, and insulin resistance during pregnancy. However, this disease includes not only changes related to metabolic distress but also placental immunoendocrine adaptations, resulting in harmful effects to the mother and fetus. In this review, we focus on the placenta as an immuno-endocrine organ that can recognize and respond to the hyperglycemic environment. It synthesizes diverse chemicals that play a role in inflammation, innate defense, endocrine response, oxidative stress, and angiogenesis, all associated with different perinatal outcomes.


Assuntos
Diabetes Gestacional , Células Endoteliais , Feto , Hiperglicemia , Placenta , Diabetes Gestacional/imunologia , Diabetes Gestacional/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Feminino , Feto/imunologia , Feto/metabolismo , Humanos , Hiperglicemia/imunologia , Hiperglicemia/metabolismo , Placenta/imunologia , Placenta/metabolismo , Placenta/patologia , Gravidez
6.
J Gen Virol ; 102(8)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34410903

RESUMO

An infectious agent's pathogenic and transmission potential is heavily influenced by early events during the asymptomatic or subclinical phase of disease. During this phase, the presence of infectious agent may be relatively low. An important example of this is Zika virus (ZIKV), which can cross the placenta and infect the foetus, even in mothers with subclinical infections. These subclinical infections represent roughly 80 % of all human infections. Initial ZIKV pathogenesis studies were performed in type I interferon receptor (IFNAR) knockout mice. Blunting the interferon response resulted in robust infectivity, and increased the utility of mice to model ZIKV infections. However, due to the removal of the interferon response, the use of these models impedes full characterization of immune responses to ZIKV-related pathologies. Moreover, IFNAR-deficient models represent severe disease whereas less is known regarding subclinical infections. Investigation of the anti-viral immune response elicited at the maternal-foetal interface is critical to fully understand mechanisms involved in foetal infection, foetal development, and disease processes recognized to occur during subclinical maternal infections. Thus, immunocompetent experimental models that recapitulate natural infections are needed. We have established subclinical intravaginal ZIKV infections in mice and guinea pigs. We found that these infections resulted in: the presence of both ZIKV RNA transcripts and infectious virus in maternal and placental tissues, establishment of foetal infections and ZIKV-mediated CXCL10 expression. These models will aid in discerning the mechanisms of subclinical ZIKV mother-to-offspring transmission, and by extension can be used to investigate other maternal infections that impact foetal development.


Assuntos
Feto , Placenta , Complicações Infecciosas na Gravidez , Infecção por Zika virus/virologia , Zika virus , Animais , Chlorocebus aethiops , Feminino , Feto/imunologia , Feto/virologia , Cobaias , Humanos , Transmissão Vertical de Doenças Infecciosas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Placenta/imunologia , Placenta/virologia , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Células Vero , Zika virus/imunologia , Zika virus/patogenicidade
7.
Reprod Toxicol ; 104: 134-142, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34324966

RESUMO

AZD1222 (ChAdOx1 nCoV-19) is a COVID-19 vaccine that is not yet licensed for use during pregnancy. To support the inclusion of pregnant and breastfeeding people in AZD1222 clinical studies, a non-clinical developmental and reproductive toxicity study was performed to evaluate its effects on fertility and reproductive processes of female CD-1 mice during the embryofetal development phase, and postnatal outcomes during the littering phase. Immunogenicity assessments were also made in dams, fetuses, and pups. There were no vaccine-related unscheduled deaths throughout the study. Furthermore, there were no vaccine-related effects on female reproduction, fetal or pup survival, fetal external, visceral, or skeletal findings, pup physical development, and no abnormal gross pathology findings in pups or dams. Antibody responses raised in dams were maintained throughout gestation and postnatal periods, and seroconversion in fetuses and pups indicate placental and lactational transfer of immunoglobulins. Together with clinical data from non-pregnant people, these results support the inclusion of pregnant and breastfeeding people in AZD1222 clinical studies.


Assuntos
Anticorpos Antivirais/sangue , Vacinas contra COVID-19/administração & dosagem , Imunogenicidade da Vacina , Vacinação , Animais , Biomarcadores/sangue , Vacinas contra COVID-19/toxicidade , Feminino , Feto/efeitos dos fármacos , Feto/imunologia , Feto/metabolismo , Idade Gestacional , Lactação/imunologia , Lactação/metabolismo , Troca Materno-Fetal , Camundongos , Placenta/imunologia , Placenta/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Medição de Risco , Soroconversão
8.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201864

RESUMO

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT. We performed a retrospective study that included pregnant women, their newborns, and placentas. It comprised 23 FNAIT cases, of which nine were newly diagnosed (14 samples) and 14 were antenatally treated with intravenous immune globulins (IVIg) (21 samples), and 20 controls, of which 10 had anti-HLA-class I antibodies. Clinical information was collected from medical records. Placental samples were stained for complement activation markers (C1q, C4d, SC5b-9, and mannose-binding lectin) using immunohistochemistry. Histopathology was examined according to the Amsterdam criteria. A higher degree of C4d deposition was present in the newly diagnosed FNAIT cases (10/14 samples), as compared to the IVIg-treated FNAIT cases (2/21 samples, p = 0.002) and anti-HLA-negative controls (3/20 samples, p = 0.006). A histopathological examination showed delayed maturation in four (44%) placentas in the newly diagnosed FNAIT cases, five (36%) in the IVIg-treated FNAIT cases, and one in the controls (NS). C4d deposition at the syncytiotrophoblast was present in combination with low-grade villitis of unknown etiology in three newly diagnosed FNAIT cases that were born SGA. We conclude that a higher degree of classical pathway-induced complement activation is present in placentas from pregnancies with untreated FNAIT. This may affect placental function and fetal growth.


Assuntos
Ativação do Complemento/imunologia , Feto/patologia , Antígenos de Histocompatibilidade Classe I/imunologia , Imunoglobulinas Intravenosas/imunologia , Placenta/patologia , Trombocitopenia Neonatal Aloimune/patologia , Adulto , Anticorpos/imunologia , Estudos de Casos e Controles , Feminino , Feto/imunologia , Humanos , Recém-Nascido , Masculino , Placenta/imunologia , Gravidez , Estudos Retrospectivos , Trombocitopenia Neonatal Aloimune/imunologia
9.
Front Immunol ; 12: 688987, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276679

RESUMO

Memory B cells play an important role in immunity to pathogens as these cells are poised to rapidly differentiate into antibody-secreting cells upon antigen re-encounter. Memory B cells also develop over the course of HLA-sensitization during pregnancy and transplantation. In this review, we discuss the potential contribution of memory B cells to pregnancy sensitization as well as the impact of these cells on transplant candidacy and outcomes. We start by summarizing how B cell subsets are altered in pregnancy and discuss what is known about HLA-specific B cell responses given our current understanding of fetal antigen availability in maternal secondary lymphoid tissues. We then review the molecular mechanisms governing the generation and maintenance of memory B cells during infection - including the role of T follicular helper cells - and discuss the experimental evidence for the development of these cells during pregnancy. Finally, we discuss how memory B cells impact access to transplantation and transplant outcomes for a range of transplant recipients.


Assuntos
Linfócitos B/imunologia , Memória Imunológica , Gravidez/imunologia , Animais , Anticorpos/imunologia , Feminino , Feto/imunologia , Antígenos HLA/imunologia , Humanos , Isoantígenos/imunologia
10.
Reprod Domest Anim ; 56(9): 1243-1253, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34174122

RESUMO

Retention of foetal membranes (RFM) is a major reproductive disorder in dairy cows. An appropriate immune response is important for a physiological expulsion of the foetal membranes at parturition. Our study aims to provide a deeper insight into characteristics of foetal and maternal macrophages in bovine term placenta. We used transmission electron microscopy (TEM), immunohistochemistry and semi-quantitative RT-PCR to provide a deeper insight into characteristics of foetal and maternal macrophages in bovine term placenta. Semi-quantitative RT-PCR was used to define macrophage polarization in foetal and maternal compartments of normal term placenta. Gene expression of factors involved in M1 polarization [interferon regulatory factor-5 (IRF5), interleukin (IL)-12A, IL12B] and in M2 polarization (IL10) were studied. Ultrastructurally, foetal macrophages showed an irregular shape and large vacuoles, whereas the maternal macrophages were spindle shaped. By immunohistochemistry, macrophages were identified by a strong staining with the lysosomal marker Lysosome-associated membrane glycoprotein 1 (LAMP-1), while myofibroblast in the maternal stroma was positive for alpha-smooth muscle actin. We used the LAMP-1 marker to compare the density of foetal stromal macrophages in placentas of cows with RFM and in controls, but no statistically significant difference was observed. RT-PCR showed a higher expression of all studied genes in the maternal compartment of the placenta and generally a higher expression of M1-, compared to M2-associated genes. Our results indicated that at parturition placental macrophages predominantly show the pro-inflammatory M1 polarization. The higher expression of all the target genes in the maternal compartment may denote that maternal macrophages in bovine term placenta are more frequent than foetal macrophages.


Assuntos
Feto/citologia , Macrófagos/fisiologia , Placenta/citologia , Animais , Bovinos , Feminino , Feto/imunologia , Macrófagos/ultraestrutura , Parto , Placenta/imunologia , Gravidez , Transcriptoma
11.
Immunology ; 163(3): 237-238, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34131917

RESUMO

The fetal immune system is distinguishable from the adult immune system by a higher degree of tolerance to foreign antigens. This tolerance is important for fetal development within the 'foreign' maternal environment, and during birth when barrier surfaces are first colonized by microbiota. Immune responses against the wave of newly colonizing microbiota would cause massive damage to barrier tissues, so neonates need suppressed immune responses and instead rely on maternal antibodies for protection. It is becoming clear that the early-life establishment of tolerance could impact immune homeostasis and predisposition to autoimmune diseases throughout life. However, it is not well understood how and when perinatal tolerogenic immune responses switch towards adult-like effector immune responses. Here, we present a new report on the differences between cells from perinatal umbilical cord blood (UCB) and adult peripheral blood mononuclear cells (PBMC), which give mechanistic insights into fetal tolerogenic responses.


Assuntos
Sangue Fetal/imunologia , Feto/imunologia , Tolerância Imunológica/imunologia , Leucócitos Mononucleares/imunologia , Gravidez/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Comunicação Celular , Diferenciação Celular , Feminino , Desenvolvimento Fetal , Humanos , Imunidade Materno-Adquirida , Recém-Nascido
12.
Transfusion ; 61(6): 1908-1915, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33938570

RESUMO

BACKGROUND: The anti-M antibody can lead to hemolytic disease of the fetus and newborn (HDFN) and adverse fetal outcomes, especially in the Asian population. However, fetal erythropoiesis resulting from M alloimmunization needs further investigation. STUDY DESIGN AND METHODS: We analyzed erythropoiesis in eight fetuses with M alloimmunization and compared them with the fetuses affected by anti-D. They were matched as pairs according to the gestational age of diagnosis and the hematocrit before treatment. Paired t-tests or paired Wilcoxon rank-sum tests were conducted to compare the difference in the cord blood indexes. Pearson correlation analysis was used to evaluate the correlativity between hematocrit and the reticulocyte percentage in the two groups. RESULTS: The fetuses in the MN group had lower reticulocyte count and percentage than those in the RhD group (p < .05). All of the fetal reticulocyte production indexes (RPIs) in the MN group were less than 2, indicating an inadequate hemopoietic response to anemia, while the majority of the RPIs in the RhD group (85.7%) were significantly higher (p = .003), with 6 cases greater than 2.5. Hematocrit was negatively correlated with reticulocyte percentage (y = 54.7-171.7x, r2  = 0.825, p = .005) in the RhD group, while no significant correlation was found in the MN group. No difference in the number of IUT, interval, or the fetal outcome was found between the two groups. CONCLUSION: Fetal reticulocytopenia provided direct evidence of an inadequate hemopoietic response in HDFN due to anti-M, leading to hyporegenerative anemia. Once the IgG component of anti-M is detected, close monitoring should be considered.


Assuntos
Anemia/imunologia , Eritroblastose Fetal/imunologia , Feto/imunologia , Imunoglobulina M/imunologia , Isoanticorpos/imunologia , Adulto , Anemia/etiologia , Anemia/fisiopatologia , Anemia/terapia , Transfusão de Sangue Intrauterina , Eritroblastose Fetal/fisiopatologia , Eritroblastose Fetal/terapia , Eritropoese , Feminino , Feto/fisiopatologia , Humanos , Recém-Nascido , Masculino , Gravidez , Reticulocitose , Imunoglobulina rho(D)/imunologia , Resultado do Tratamento , Adulto Jovem
13.
Front Immunol ; 12: 638435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936052

RESUMO

Immunologic tolerance refers to a state of immune nonreactivity specific to particular antigens as an important issue in the field of transplantation and the management of autoimmune diseases. Tolerance conceptually originated from Owen's observation of blood cell sharing in twin calves. Owen's conceptual framework subsequently constituted the backbone of Medawar's "actively acquired tolerance" as the major tenet of modern immunology. Based upon this knowledge, the delivery of genetically distinct hematopoietic stem cells into pre-immune fetuses represented a novel and unique approach to their engraftment without the requirement of myeloablation or immunosuppression. It might also make fetal recipients commit donor alloantigens to memory of their patterns as "self" so as to create a state of donor-specific tolerance. Over the years, the effort made experimentally or clinically toward in utero marrow transplantation could not reliably yield sufficient hematopoietic chimerism for curing candidate diseases as anticipated, nor did allogeneic graft tolerance universally develop as envisaged by Medawar following in utero exposure to various forms of alloantigens from exosomes, lymphocytes or marrow cells. Enduring graft tolerance was only conditional on a state of significant hematopoietic chimerism conferred by marrow inocula. Notably, fetal exposure to ovalbumin, oncoprotein and microbial antigens did not elicit immune tolerance, but instead triggered an event of sensitization to the antigens inoculated. These fetal immunogenic events might be clinically relevant to prenatal imprinting of atopy, immune surveillance against developmental tumorigenesis, and prenatal immunization against infectious diseases. Briefly, the immunological consequences of fetal exposure to foreign antigens could be tolerogenic or immunogenic, relying upon the type or nature of antigens introduced. Thus, the classical school of "actively acquired tolerance" might oversimplify the interactions between developing fetal immune system and antigens. Such interactions might rely upon fetal macrophages, which showed up earlier than lymphocytes and were competent to phagocytose foreign antigens so as to bridge toward antigen-specific adaptive immunity later on in life. Thus, innate fetal macrophages may be the potential basis for exploring how the immunological outcome of fetal exposure to foreign antigens is determined to improve the likelihood and reliability of manipulating fetal immune system toward tolerization or immunization to antigens.


Assuntos
Feto/imunologia , Sistema Imunitário/embriologia , Tolerância Imunológica/imunologia , Isoantígenos/imunologia , Animais , Feminino , Humanos , Gravidez
14.
Front Immunol ; 12: 624136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995348

RESUMO

Fetal anemia is common in malaria-endemic areas and a risk factor for anemia as well as mortality during infancy. Placental malaria (PM) and red cell abnormalities have been proposed as possible etiologies, but the relationship between PM and fetal anemia has varied in earlier studies, and the role of red cell abnormalities has not been studied in malaria-endemic areas. In a Tanzanian birth cohort study designed to elucidate the pathogenesis of severe malaria in young infants, we performed a cross-sectional analysis of risk factors for fetal anemia. We determined PM status, newborn red cell abnormalities, and maternal and cord blood levels of iron regulatory proteins, erythropoietin (EPO), cytokines and cytokine receptors. We examined the relationship between these factors and fetal anemia. Fetal anemia was present in 46.2% of the neonates but was not related to PM. Maternal iron deficiency was common (81.6%), most frequent in multigravidae, and interacted with parity to modify risk of fetal anemia, but it was not directly related to risk. Among offspring of iron-deficient women, the odds of fetal anemia increased with fetal α+-thalassemia, as well as these patterns of cord blood cytokines: increased cord IL-6, decreased TNF-RI, and decreased sTfR. The EPO response to fetal anemia was low or absent and EPO levels were significantly decreased in newborns with the most severe anemia. This study from an area of high malaria transmission provides evidence that 1) fetal α+-thalassemia and cytokine balance, but not PM at delivery, are related to fetal anemia; 2) maternal iron deficiency increases the risk that other factors may cause fetal anemia; and 3) fetal anemia has a multifactorial etiology that may require a variety of interventions, although measures that reduce maternal iron deficiency may be generally beneficial.


Assuntos
Anemia/etiologia , Citocinas/sangue , Eritropoetina/sangue , Doenças Fetais/etiologia , Feto/metabolismo , Malária/parasitologia , Placenta/parasitologia , Complicações Parasitárias na Gravidez/parasitologia , Talassemia alfa/complicações , Adulto , Anemia/sangue , Anemia/imunologia , Anemia/parasitologia , Biomarcadores/sangue , Estudos Transversais , Feminino , Doenças Fetais/sangue , Doenças Fetais/imunologia , Doenças Fetais/parasitologia , Feto/imunologia , Hemoglobinas/metabolismo , Humanos , Recém-Nascido , Ferro/sangue , Ferro/deficiência , Malária/sangue , Malária/imunologia , Masculino , Saúde Materna , Paridade , Placenta/imunologia , Placenta/metabolismo , Gravidez , Complicações Parasitárias na Gravidez/sangue , Complicações Parasitárias na Gravidez/imunologia , Medição de Risco , Fatores de Risco , Tanzânia , Transferrina/metabolismo , Adulto Jovem , Talassemia alfa/sangue , Talassemia alfa/imunologia
15.
Sci Rep ; 11(1): 10331, 2021 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-33990635

RESUMO

Chorioamnionitis, inflammation of fetal membranes, is an important cause of preterm birth and a risk factor for the development of adverse neonatal outcomes including sepsis and intestinal pathologies. Intestinal bile acids (BAs) accumulation and hepatic cytokine production are involved in adverse intestinal outcomes. These findings triggered us to study the liver and enterohepatic circulation (EHC) following intra-amniotic (IA) lipopolysaccharide (LPS) exposure. An ovine chorioamnionitis model was used in which circulatory cytokines and outcomes of the liver and EHC of preterm lambs were longitudinally assessed following IA administration of 10 mg LPS at 5, 12 or 24h or 2, 4, 8 or 15d before preterm birth. Hepatic inflammation was observed, characterized by increased hepatic cytokine mRNA levels (5h - 2d post IA LPS exposure) and increased erythropoietic clusters (at 8 and 15 days post IA LPS exposure). Besides, 12h after IA LPS exposure, plasma BA levels were increased, whereas gene expression levels of several hepatic BA transporters were decreased. Initial EHC alterations normalized over time. Concluding, IA LPS exposure induces significant time-dependent changes in the fetal liver and EHC. These chorioamnionitis induced changes have potential postnatal consequences and the duration of IA LPS exposure might be essential herein.


Assuntos
Corioamnionite/imunologia , Circulação Êntero-Hepática/imunologia , Feto/irrigação sanguínea , Hepatite/imunologia , Nascimento Prematuro/imunologia , Animais , Ácidos e Sais Biliares/sangue , Ácidos e Sais Biliares/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Corioamnionite/sangue , Corioamnionite/patologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Feto/imunologia , Regulação da Expressão Gênica/imunologia , Hepatite/sangue , Hepatite/patologia , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/imunologia , Fígado/imunologia , Fígado/patologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Gravidez , Nascimento Prematuro/sangue , Carneiro Doméstico , Fatores de Tempo
16.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805739

RESUMO

As most recently demonstrated by the SARS-CoV-2 pandemic, congenital and perinatal infections are of significant concern to the pregnant population as compared to the general population. These outcomes can range from no apparent impact all the way to spontaneous abortion or fetal infection with long term developmental consequences. While some pathogens have developed mechanisms to cross the placenta and directly infect the fetus, other pathogens lead to an upregulation in maternal or placental inflammation that can indirectly cause harm. The placenta is a temporary, yet critical organ that serves multiple important functions during gestation including facilitation of fetal nutrition, oxygenation, and prevention of fetal infection in utero. Here, we review trophoblast cell immunology and the molecular mechanisms utilized to protect the fetus from infection. Lastly, we discuss consequences in the placenta when these protections fail and the histopathologic result following infection.


Assuntos
Imunidade , Placenta/imunologia , Placenta/virologia , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Viroses/imunologia , Vírus/imunologia , Feminino , Feto/imunologia , Feto/virologia , Humanos , Placenta/patologia , Gravidez , Trofoblastos/imunologia , Trofoblastos/virologia
17.
J Allergy Clin Immunol ; 148(3): 843-857.e6, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33684437

RESUMO

BACKGROUND: Prenatal exposure to infections can modify immune development. These environmental disturbances during early life potentially alter the incidence of inflammatory disorders as well as priming of immune responses. Infection with the helminth Schistosoma mansoni is widely studied for its ability to alter immune responsiveness and is associated with variations in coinfection, allergy, and vaccine efficacy in endemic populations. OBJECTIVE: Exposure to maternal schistosomiasis during early life, even without transmission of infection, can result in priming effects on offspring immune responses to bystander antigenic challenges as related to allergic responsiveness and vaccination, with this article seeking to further clarify the effects and underlying immunologic imprinting. METHODS: Here, we have combined a model of chronic maternal schistosomiasis infection with a thorough analysis of subsequent offspring immune responses to allergy and vaccination models, including viral challenge and steady-state changes to immune cell compartments. RESULTS: We have demonstrated that maternal schistosomiasis alters CD4+ responses during allergic sensitization and challenge in a skewed IL-4/B-cell-dominant response to antigenic challenge associated with limited inflammatory response. Beyond that, we have uncovered previously unidentified alterations to CD8+ T-cell responses during immunization that are dependent on vaccine formulation and have functional impact on the efficacy of vaccination against viral infection in a murine hepatitis B virus model. CONCLUSION: In addition to steady-state modifications to CD4+ T-cell polarization and B-cell priming, we have traced these modified CD8+ responses to an altered dendritic cell phenotype sustained into adulthood, providing evidence for complex priming effects imparted by infection via fetomaternal cross talk.


Assuntos
Efeitos Tardios da Exposição Pré-Natal/imunologia , Hipersensibilidade Respiratória/imunologia , Esquistossomose/imunologia , Alérgenos/imunologia , Animais , Linfócitos B/imunologia , Células Cultivadas , Células Dendríticas/imunologia , Feminino , Feto/imunologia , Perfilação da Expressão Gênica , Imunização , Pulmão/imunologia , Linfonodos/imunologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ovalbumina/imunologia , Gravidez , Hipersensibilidade Respiratória/genética , Schistosoma mansoni , Baço/imunologia , Linfócitos T/imunologia
19.
Transfusion ; 61(5): 1350-1354, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33650699

RESUMO

FcRn, a non-classical Fc gamma (γ) receptor (FcγR) with near ubiquitous expression, plays key roles in disease pathogenesis and progression though immunoglobulin G (IgG) transport, IgG recycling, and IgG-immune complex clearance. FcRn function can be inhibited using IgG-based and non-IgG-based antagonists, by exploiting the pH-dependent binding affinity of FcRn for the IgG Fc region. FcRn therapeutics have shown promise in murine models and human clinical trials for autoimmune diseases and maternal-fetal immune cytopenias; they appear safe, well-tolerated, and reduce circulating IgG levels. Compared to traditional therapeutics, inhibiting FcRn has fewer adverse side effects and represents a new approach that is less invasive, time-consuming, and costly.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptores Fc/antagonistas & inibidores , Animais , Doenças Autoimunes/imunologia , Autoimunidade/efeitos dos fármacos , Desenvolvimento de Medicamentos , Feminino , Feto/imunologia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Imunoglobulina G/imunologia , Terapia de Alvo Molecular , Gravidez , Púrpura Trombocitopênica Idiopática/imunologia , Receptores Fc/imunologia
20.
Anim Sci J ; 92(1): e13541, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33728713

RESUMO

Toll-like receptors (TLRs) participate in regulation of adaptive immune responses, and lymph nodes play key roles in the initiation of immune responses. There is a tolerance to the allogenic fetus during pregnancy, but it is unclear that expression of TLR signaling is in ovine lymph node during early pregnancy. In this study, lymph nodes were sampled from day 16 of nonpregnant ewes and days 13, 16, and 25 of pregnant ewes, and the expressions of TLR family (TLR2, TLR3, TLR4, TLR5 and TLR9), adaptor proteins, including myeloid differentiation primary-response protein 88 (MyD88), tumor necrosis factor receptor associated factor 6 (TRAF6), and interleukin-1-receptor-associated kinase 1 (IRAK1), were analyzed through real-time quantitative polymerase chain reaction, Western blot, and immunohistochemistry analysis. The results showed that mRNA and protein levels of TLR2, TLR3, TLR4, TRAF6, and MyD88 were upregulated in the maternal lymph node, but TLR5, TLR9, and IRAK1 were downregulated during early pregnancy. In addition, MyD88 protein was located in the subcapsular sinus and lymph sinuses. Therefore, it is suggested that early pregnancy induces changes in TLR signaling in maternal lymph node, which may be involved in regulation of maternal immune responses in sheep.


Assuntos
Linfonodos/imunologia , Prenhez/imunologia , Ovinos/imunologia , Transdução de Sinais/imunologia , Receptores Toll-Like/imunologia , Animais , Regulação para Baixo/genética , Regulação para Baixo/imunologia , Feminino , Feto/imunologia , Expressão Gênica , Fator 88 de Diferenciação Mieloide/imunologia , Fator 88 de Diferenciação Mieloide/metabolismo , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator 6 Associado a Receptor de TNF/imunologia , Fator 6 Associado a Receptor de TNF/metabolismo , Receptores Toll-Like/metabolismo , Regulação para Cima/genética , Regulação para Cima/imunologia
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