NK cells in the female reproductive tract (FRT) acquire an effector transcriptional program during menstruation
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ABSTRACT:
PROVIDER: PRJNA1265255 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33630360_1.fastq.gz | Fastqsanger.gz | |||
| SRR33630360_2.fastq.gz | Fastqsanger.gz | |||
| SRR33630361_1.fastq.gz | Fastqsanger.gz | |||
| SRR33630361_2.fastq.gz | Fastqsanger.gz | |||
| SRR33630362_1.fastq.gz | Fastqsanger.gz |
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Project description:To evaluate the impact of the menstrual cycle on the transcriptional programs of NK cells in the female reproductive tract (FRT), we compared NK cells (Live lymphocytes, CD45.2+, DX5+, NK1.1+, Ly6G-, CD3-, CD19-) from the spleen and FRT of female C57BL/6J mice either treated with medroxy-progesterone acetate (MPA) or on day 8 of the pseudopregnancy / menstruation protocol. Prior to euthanasia, mice were injected intravenously with anti-CD45 antibody to discern between tissue and circulating NK cells in the FRT, with only tissue-resident cells sorted for analysis. Sorted splenic NK cells were not separated based on CD45 staining. The results indicate that FRT NK cells isolated on day 8 of the pseudopregnancy / menstruation protocol express genes associated with NK cell effector responses compared to FRT NK cells in mice treated with MPA and compared to splenic NK cells in both models.
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Project description:In order to better understand the female reproductive tract (FRT) we conducted a systematic, comprehensive investigation of the FRT in a tssue-specific manner at three time points relative to mating. By characterizing the transcriptional relationships among discrete FRT tissues across time we advance the understanding of the molecular genetics of FRT functions.
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Project description:Fertility depends on the coordination of complex interactions between male and female reproductive proteins inside the female reproductive tract (FRT). These interactions mediate a suite of changes in female behavior, morphology, and physiology after mating, yet little is known about how the molecular environment of the FRT may differ among species and coordinate species-specific female post-mating responses. We used semi-quantitative proteomics to compare the FRT protein composition between virgin and mated females in Drosophila melanogaster. These results are compared to those from quantitative TMT proteomic analyses of the mating-induced changes in D. simulans and D. mauritiana, and after conspecific and heterospecific inseminations. Our study highlights the value of using quantitative proteomics approaches to study the molecular composition of the FRT environment, and how its divergence may inform mechanistic studies of post-mating pre-zygotic reproductive isolation between species.
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Project description:The female reproductive tract (FRT) is vulnerable to sexually transmitted infections and therefore a well-tuned immune surveillance system is crucial for maintaining a healthy FRT. However, our understanding of the factors that impact viral infection of the FRT and the host response are not well understood. In this work, we investigate the role of a hormonally regulated type I interferon, IFN epsilon, in control of Zika virus (ZIKV) infection of the FRT. We demonstrate that IFN epsilon has anti-ZIKV properties using a combination of IFN epsilon KO mice, blockade of endogenous IFN epsilon by neutralising Abs and rescue of IFN epsilon KO mice by recombinant IFN epsilon administered directly to the FRT.
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Project description:Interferon ε (IFNε), a unique type I IFN, is thought to protect the host against sexually transmitted infections. Unlike conventional type I IFNs (e.g., IFNα/β), whose expression is undetectable at baseline, IFNε expression is detectable in the epithelium of mucosal tissues, particularly the female reproductive tract (FRT). We found that IFNε expression was not limited to epithelial cells at the FRT. Importantly, in contrast to previous reports, IFNε expression in plasmacytoid dendritic cells and primary cervical epithelial cells was induced by viral infection and by activation of TLR3 or 4 in PBMCs. Induction of IFNε mRNAs was also found in cervicovaginal tissues (CVT) of Zika virus (ZIKV)-infected mice. Mice with IFNε deficiency (Ifnε-/-) did not have impaired induction of interferon-stimulated genes except IFNl, but had altered epithelial and collagen structure in the CVT. Ifnε-/- mice exhibited increased susceptibility to ZIKV infection via an intravaginal route but not via a subcutaneous route, indicating that the protective effect of IFNe was specific to the FRT. Infected Ifnε-/- mice had higher and more sustained viral loads than infected wild-type (WT) mice. Detection of ZIKV infection by single molecule in situ hybridization confirmed that virus spread faster in Ifnε-/- mice than in WT mice. Recombinant murine IFNε protected Ifnar1-/- mice against ZIKV infection when administered through an intravaginal route but not when administered through a subcutaneous route, indicating that the specific role of IFNe at the FRT is independent of IFNAR1 signaling. Our findings indicate that IFNε mediates a novel FRT-specific protective effect on mucosal immunity that limits Zika virus spread.
2023-05-11 | GSE228359 | GEO
Project description:Fertility depends on the progression of complex and coordinated postmating processes within the extracellular luminal environment of the female reproductive tract (FRT). To achieve a more comprehensive level of knowledge regarding female-derived proteins available to interact with the ejaculate, we utilized semiquantitative mass spectrometry-based proteomics to study the composition of the FRT tissue and, separately, the luminal fluid, before and after mating in Drosophila melanogaster. Our approach leveraged whole-fly isotopic labelling to delineate between female proteins and those transferred from males in the ejaculate. The dynamic mating-induced proteomic changes in the extracellular FRT luminal fluid further informs our understanding of secretory mechanisms of the FRT and serves as a foundation for establishing the roles of ejaculate-female interactions in fertility.
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Project description:HIV-1 sexual transmission occurs mainly via mucosal semen exposures. In the female reproductive tract (FRT), seminal plasma (SP) induces physiological modifications, including inflammation. An effective HIV-1 vaccine should elicit mucosal immunity. However, modifications of vaccine responses by the local environment remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized the impact of HIV-1+ SP intravaginal exposure on the local immune responses of nonhuman primates. Multiple HIV-1+ SP exposures did not impact the anti-MVA antibody responses. However, SP exposures revealed an anti-MVA responses mediated by CD4+ T cells, which was not observed in the control group. Multi-parameter approaches clearly identified the cervix as the most impacted compartment in the FRT. The frequency and the quality of specific anti-MVA CD8+ T cell responses increased in the FRT exposed to SP. Furthermore SP exposures induced a local cell recruitment of antigen presenting cells, especially CD11c+ cells and CD8+ T cell recruitment in the FRT draining lymph nodes. CD11c+ cell recruitment was associated with upregulation of inflammation-related gene expression after SP exposures in the cervix. We thus highlight the fact that physiological conditions, such as SP exposures, should be taken into consideration to test and to improve vaccine efficacy against HIV-1 and other sexually transmitted infections.
2019-02-12 | E-MTAB-7639 | biostudies-arrayexpress
Project description:Id2-deficient NK cells acquire a naïve-like fate
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Project description:The female reproductive tract is one of the major mucosal invasion site of HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune responses in the female reproductive tract after systemic vaccination remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized specific immune responses in all compartments of the female reproductive tract (FRT) of non-human primates after systemic vaccination. Memory T cells were preferentially found in the lower tract (vagina and cervix), whereas antigen-presenting cells and innate lymphoid cells were mainly located in the upper tract (uterus and fallopian tubes). This compartmentalisation of immune cells in the FRT was supported by transcriptomic analyses and correlation network. Polyfunctional MVA-specific CD8+ T cells were detected in the blood, lymph nodes, vagina, cervix, uterus and fallopian tubes. Anti-MVA IgG and IgA were detected in cervicovaginal fluid after a second vaccine dose. Systemic vaccination with an MVA vector thus elicits cellular and antibody responses in the female reproductive tract.
2017-06-09 | E-MTAB-5663 | biostudies-arrayexpress
Project description:Fertility depends, in part, on interactions between male and female reproductive proteins inside the female reproductive tract (FRT) that mediate postmating changes in female behavior, morphology, and physiology. Coevolution between interacting proteins within species may drive reproductive incompatibilities between species, yet the mechanisms underlying postmating-prezygotic isolating barriers remain poorly resolved. Here, we used quantitative proteomics in sibling Drosophila species to investigate the molecular composition of the FRT environment and its role in mediating species-specific postmating responses. We found that (1) FRT proteomes in D. simulans and D. mauritiana virgin females express unique combinations of secreted proteins and are enriched for distinct functional categories, (2) mating induces substantial changes to the FRT proteome in D. mauritiana but not in D. simulans, and (3) the D. simulans FRT proteome exhibits limited postmating changes irrespective of whether females mate with conspecific or heterospecific males, suggesting an active female role in mediating reproductive interactions. Our study suggests that divergence in the FRT extracellular environment and postmating response contribute to previously described patterns of postmating-prezygotic isolation and the maintenance of species boundaries.
2020-06-25 | PXD017708 | Pride