Single-cell transcriptomic analysis of decidual immune cell landscape in the occurrence of adverse pregnancy outcomes induced by Toxoplasma gondii infection
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ABSTRACT:
PROVIDER: PRJNA1069667 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27743421_1.fastq.gz | Fastqsanger.gz | |||
| SRR27743421_2.fastq.gz | Fastqsanger.gz | |||
| SRR27743422_1.fastq.gz | Fastqsanger.gz | |||
| SRR27743422_2.fastq.gz | Fastqsanger.gz |
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Project description:Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that can lead to adverse pregnancy outcomes, particularly in early pregnancy. Previous studies have illustrated the landscape of decidual immune cells. However, the landscape of decidual immune cells in the maternal–fetal microenvironment during T. gondii infection remains unknown. In this study, we employed single-cell RNA sequencing to analyze the changes in human decidual immune cells following T. gondii infection. Our results showed that the proportion of 17 decidual immune cell clusters and the expression levels of 21 genes were changed after T. gondii infection. Differential gene analysis demonstrated that T. gondii infection induced the differential expression of 279, 312, and 380 genes in decidual NK, dMφ, and dT cells, respectively. Our findings first revealed that several previously unknown molecules in decidual immune cells changed following T. gondii infection. This result revealed that the function of maternal–fetal immune tolerance declined, whereas the killing ability of decidual immune cells enhanced, eventually contributing to the occurrence of adverse pregnancy outcomes. The results of this study provide a valuable resource for uncovering several novel molecules that play an important role in the occurrence of abnormal pregnancy outcomes induced by T. gondii infection.
2024-05-17 | GSE254302 | GEO
Project description:A Toxoplasma gondii infection during pregnancy can result in spontaneous abortion, preterm labor, or congenital fetal defects. The decidual immune system plays a critical role in regulating the immune micro-environment and in the induction of immune tolerance. To better understand the factors that mediate the decidual immune response associated with the T. gondii infection, a large-scale study employing TMT proteomics was conducted to characterize the differential decidual immune proteomes from infected and uninfected human decidual immune cells samples. The decidual immune cells from 105 human voluntary abortion tissues were purified, and of the 5510 unique proteins identified, 181 proteins were found to be differentially abundant (>1.2-fold cutoff, P＜0.05) in the T. gondii-infected decidual immune cells. 11 proteins of 181 differentially expressed proteins associated with trophoblast invasion, placental development, intrauterine fetal growth, and immune tolerance were verified using a quantitative real-time polymerase chain reaction and western blotting. This systematic research identified a broad range of immune factors in human decidual immune cells, shedding a new insight into the decidual immune molecular mechanism for abnormal pregnancy outcomes associated with T. gondii infection.
2018-07-27 | PXD008448 | Pride
Project description:BackgroundToxoplasma gondii infection during pregnancy can lead to fetal defect(s) or congenital complications. The inhibitory molecule B7-H4 expressed on decidual macrophages (dMφ) plays an important role in maternal-fetal tolerance. However, the effect of B7-H4 on the function of dMφ during T. gondii infection remains unclear.MethodsChanges in B7-H4 expression on dMφ after T. gondii infection were explored both in vivo and in vitro. B7-H4-/- pregnant mice (pregnant mice with B7-H4 gene knockout) and purified primary human dMφ treated with B7-H4 neutralizing antibody were used to explore the role of B7-H4 signaling on regulating the membrane molecules, synthesis of arginine metabolic enzymes and cytokine production by dMφ with T. gondii infection. Also, adoptive transfer of dMφ from wild-type (WT) pregnant mice or B7-H4-/- pregnant mice to infected B7-H4-/- pregnant mice was used to examine the effect of B7-H4 on adverse pregnancy outcomes induced by T. gondii infection.ResultsThe results illustrated that B7-H4-/- pregnant mice infected by T. gondii had poorer pregnancy outcomes than their wild-type counterparts. The expression of B7-H4 on dMφ significantly decreased after T. gondii infection, which resulted in the polarization of dMφ from the M2 toward the M1 phenotype by changing the expression of membrane molecules (CD80, CD86, CD163, CD206), synthesis of arginine metabolic enzymes (Arg-1, iNOS) and production of cytokines (IL-10, TNF-α) production. Also, we found that the B7-H4 downregulation after T. gondii infection increased iNOS and TNF-α expression mediated through the JAK2/STAT1 signaling pathway. In addition, adoptive transfer of dMφ from a WT pregnant mouse donor rather than from a B7-H4-/- pregnant mouse donor was able to improve adverse pregnancy outcomes induced by T. gondii infection.ConclusionsThe results demonstrated that the downregulation of B7-H4 induced by T. gondii infection led to the dysfunction of decidual macrophages and contributed to abnormal pregnancy outcomes. Moreover, adoptive transfer of B7-H4+ dMφ could improve adverse pregnancy outcomes induced by T. gondii infection.
| S-EPMC9746109 | biostudies-literature
Project description:ObjectiveQuantified risks of congenital Toxoplasma gondii infection and abnormal pregnancy outcomes following primary maternal infection were evaluated with meta- analysis based on published studies.MethodsThe related literatures were searched in multiple literature databases regardless of languages. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the risks of vertical transmission of Toxoplasma gondii and abnormal pregnancy outcomes following primary maternal infection with meta-analysis.Results53 of the 2632 searched literatures were included in our analysis. The incidence of abnormal pregnancy outcomes in T. gondii infected pregnant women (infected group) was significantly higher than that in the uninfected pregnant women (control group) (OR = 5.10; 95% CI, 3.85-6.75). Toxoplasma gondii infection rate in the abnormal-pregnancy-outcome group was significantly higher than in the normal-pregnancy group (OR = 3.71; 95% CI, 3.31-4.15). The pooled rate of vertical transmission was 20% (95% CI, 15%-26%) in maternal infection of T. gondii. The incidences of vertical transmission in women who were infected in the first, second or third trimester of pregnancy were 5% (95%CI, 2%-16%), 13% (95%CI, 7%-23%), and 32% (95%CI, 24%-41%), respectively. The rates of vertical transmission in women who were treated with spiramycin-only, PSF (pyrimethamine + sulfadiazine + folinic acid) or PS (pyrimethamine + sulfadiazine) combined with spiramycin, or other untypical treatments were 13% (95%CI, 7%-22%), 13%(95%CI, 7%-25%), and 24%(95%CI, 18%-32%), respectively.ConclusionsToxoplasma gondii infection can result in adverse pregnancy outcomes in pregnant women. The pooled rate of vertical transmission was 20% in maternal infection and the incidences of vertical transmission increased in the first, second or third trimester of pregnancy. The pooled rates of transmission in groups treated with spiramycin-only, PSF or PS combined with spiramycin, or other untypical treatments were not significantly different.
| S-EPMC4022675 | biostudies-literature
Project description:Background:Toxoplasma gondii (T. gondii) is an obligate intracellular parasite, which can affect the pregnancy outcomes in infected females by damaging the uterus, and the intrauterine environment as well as and the hypothalamus resulting in hormonal imbalance. However, the molecular mechanisms underlying the parasite-induced poor pregnancy outcomes and the key genes regulating these mechanisms remain unclear. Therefore, this study aimed to analyze the gene expression in the mouse's uterus following experimentally-induced acute infection with T. gondii RH strain. Three groups of female mice were intraperitoneally injected with tachyzoites as follow; 3 days before pregnancy (FBD6), after pregnancy (FAD6), and after implantation (FID8) as the experimental groups. Another corresponding three groups served as control, were injected with normal saline at the same time. Transcriptome analysis of the total RNA extracted from both infected and non-infected mouse uterus samples was performed using RNA sequencing (RNA-Seq). Results:The three experimental groups (FBD6, FAD6, and FID8) had a total of 4,561, 2,345, and 2,997 differentially expressed genes (DEGs) compared to the controls. The significantly upregulated and downregulated DEGs were 2,571 and 1,990 genes in FBD6, 1,042 and 1,303 genes in FAD6 and 1,162 and 1,835 genes in FID8 group, respectively. The analysis of GO annotation, and KEGG pathway showed that DEGs were mainly involved in anatomical structure development, transport, cell differentiation, embryo development, hormone biosynthetic process, signal transduction, immune system process, phagosome, pathways in cancer, and cytokine-cytokine receptor interaction pathways. Conclusion:T. gondii infection can induce global transcriptomic changes in the uterus that may cause pregnancy hypertension, destruct the intrauterine environment, and hinder the normal development of placenta and embryo. Our results may help to understand the molecular mechanisms of the acute T. gondii infection, which could promote the development of new therapeutics or prophylactics for toxoplasmosis in pregnancy.
| S-EPMC7042390 | biostudies-literature
Project description: Not available
| S-EPMC11234737 | biostudies-literature
Project description:It is suggested that decidual polymorphonuclear myeloid-derived suppressor cell (PMN-MDSCs) are a group of activated suppressive neutrophils. Decidual microenvironment can facilitate circulating neutrophils with phenotypes and functions of PMN-MDSCs. The mechanism of PMN-MDSCs differentiation induced by decidual microenvironment has not been fully understood. Here we performed whole genome expression profile of 3 decidual PMN-MDSCs and autologous neutrophils from normal early pregnancy. Total RNA were extracted. The arrays were scanned by the Agilent Scanner G2505C. There were differences of gene expression pattern between decidual PMN-MDSCs and autologous neutrophils in early normal pregnancy.
2022-05-13 | GSE192850 | GEO
Project description:Imbalance of Th1 and Th2 response at the maternal-fetal interface is considered as a radical event in the pathogenesis of immunity-related pregnant diseases. It has been demonstrated that the ROP16I, a rhoptry protein of Toxoplasma gondii, and the viable parasite with ROP16I may induce M2 macrophage polarization in host innate immunity and may be involved in the adverse pregnant outcomes. However, the mechanisms by which T. gondii-derived effectors subvert the immune tolerance in the pathology of pregnancy remain unclear. Here, we constructed the RH strain with ROP16I deletion (RH?rop16) to explore the pathogenesis of abnormal pregnancy. We found that C57BL/6 mice infected with RH?rop16 exhibited the increased resorption of fetuses and more severe adverse pathology of placentae at the early phase of gestation, as compared to the mice infected with RH wild type (RH WT) parasite. Additionally, RH?rop16 strain infection significantly promoted M1 macrophage phenotypes of CD80 and CD86, and decreased CD206 expression of M2 macrophages, with upregulation of the iNOS and downregulation of the Arg-1 expression in placental homogenates. Simultaneously, the pro-inflammatory cytokines of IL-12 and TNF-? were elevated whereas the anti-inflammatory cytokine of TGF-?1 was dampened. Moreover, the p38? mitogen-activated protein kinase (p38? MAPK) was notably phosphorylated in placental macrophages infected with both RH?rop16 and RH WT strains compared with the control. Taken together, our findings indicated that ROP16I deletion of type I RH strain may cause exacerbated adverse pregnant outcomes, which is attributable to subversion of the maternal immune tolerance due to the increased pro-inflammatory cytokines in the pregnant animals. The results also suggest that ROP16I might be a protective factor and other T. gondii-derived molecules might be involved in the M1-Th1 biased pathological process in aberrant pregnancy at the early phase of gestation.
| S-EPMC7005636 | biostudies-literature
Project description:Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) accumulate in maternal-fetal interface during pregnancy and play a role in maintenance of immune tolerance. Decreased PMN-MDSC is associated with pregnancy complications such as unexplained recurrent pregnancy loss (URPL). Whether PMN-MDSC function is different between normal pregnancy (NP) and URPL remains unexplored. Here we performed whole genome expression profile of 3 decidual PMN-MDSC from normal early pregnancy and 3 decidual PMN-MDSC from URPL. Total RNA were extracted. Cy5-labeled aRNA was hybridized and scanned on a G2505C Agilent Microarray Scanner with Agilent 0.1 XDR software. The gene expression pattern of the PMN-MDSC was significantly different between the NP group and the URPL group.
2020-06-30 | GSE139180 | GEO
Project description:Estradiol (E2) plays a crucial and intricate role during pregnancy to mediate several aspects of the pregnancy process. A perplexing phenomenon in congenital toxoplasmosis is that the severity of Toxoplasma gondii (T. gondii)-mediated adverse pregnancy outcome is closely related with time of primary maternal infection during pregnancy. In this study, the results showed that T. gondii infection in early pregnancy was more likely to induce miscarriage in mice than in late pregnancy, which may be related to inflammation of the maternal-fetal interface. Meanwhile, the T. gondii infection-induced-apoptotic rate of Tregs was higher and the expression of programmed death-1 (PD-1) on Tregs was lower in early pregnancy than in late pregnancy. As the level of E2 in mouse serum gradually increased with the development of pregnancy, we proposed that E2 may contribute to the discrepancy of Tregs at different stages of pregnancy. Thus, we investigated in vitro and in vivo effects of E2 in regulating Tregs. We found that E2 in vitro could protect Tregs against apoptosis and upregulate the expression of PD-1 on Tregs in a dose-dependent manner through ER?. Likewise, the simulated mid-pregnancy level of E2 in nonpregnant mice also alleviated the T. gondii infection-induced apoptosis of Tregs and potentiated the PD-1 expression on Tregs. Therefore, in the pathogenesis of T. gondii-induced abnormal pregnancy, E2 helped maintain the immune balance and improve the pregnancy outcome through regulating Tregs. This finding illustrates the intricate working of hormone-immune system interaction in infection-induced abnormal pregnancy.
| S-EPMC5968100 | biostudies-literature