Characterizing the Immune Infiltrates in Secondary Syphilis: Implications for Transmission and Pathology
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PROVIDER: PRJNA1237298 | ENA |
REPOSITORIES: ENA
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Project description:Provisionally accepted
2025-03-21 | GSE292160 | GEO
Project description:Background: Herbicides are environmental contaminants that have gained much attention due to the potential hazards they pose to human health. Glyphosate, the active ingredient in many commercial herbicides, is the most heavily applied herbicide worldwide. The recent rise in glyphosate application to corn and soy crops correlates positively with increased death rates due to Alzheimer's disease and other neurodegenerative disorders. Glyphosate has been shown to cross the blood-brain barrier in in vitro models, but has yet to be verified in vivo. Additionally, reports have shown that glyphosate exposure increases pro-inflammatory cytokines in blood plasma, particularly TNFα. Methods: Here, we examined whether glyphosate infiltrates the brain and elevates TNFα levels in 4-month-old C57BL/6J mice. Mice received either 125, 250, or 500 mg/kg/day of glyphosate, or a vehicle via oral gavage for 14 days. Urine, plasma, and brain samples were collected on the final day of dosing for analysis via UPLC-MS and ELISAs. Primary cortical neurons were derived from amyloidogenic APP/PS1 pups to evaluate in vitro changes in Aβ40-42 burden and cytotoxicity. RNA sequencing was performed on C57BL/6J brain samples to determine changes in the transcriptome. Results: Our analysis revealed that glyphosate infiltrated the brain in a dose-dependent manner and upregulated TNFα in both plasma and brain tissue post-exposure. Notably, glyphosate measures correlated positively with TNFα levels. Glyphosate exposure in APP/PS1 primary cortical neurons increases levels of soluble Aβ40-42 and cytotoxicity. RNAseq revealed over 200 differentially expressed genes in a dose-dependent manner and cell-type-specific deconvolution analysis showed enrichment of key biological processes in oligodendrocytes including myelination, axon ensheathment, glial cell development, and oligodendrocyte development. Conclusions: Collectively, these results show for the first time that glyphosate infiltrates the brain, elevates both the expression of TNFα and soluble Aβ, and disrupts the transcriptome in a dose-dependent manner, suggesting that exposure to this herbicide may have detrimental outcomes regarding the health of the general population.
2024-01-15 | GSE253299 | GEO
Project description:Glyphosate infiltrates the brain and increases pro-inflammatory cytokine TNFα: implications for neurodegenerative disorders
| PRJNA1064995 | ENA
Project description:BACKGROUND: Adoptive transfer of autologous regulatory T cells (Tregs) is a promising therapeutic strategy aimed at enabling immunosuppression minimization following kidney transplantation. In our phase I clinical trial of Treg cell therapy in living donor renal transplantation, the ONE Study (NCT02129881), we observed focal lymphocytic infiltrates in protocol kidney transplant biopsies that are not regularly seen in biopsies of patients receiving standard immunosuppression. METHODS: We present seven years of follow-up data on patients treated with adoptive Treg cell therapy early post-transplantation, who exhibited focal lymphocytic infiltrates on a nine-month protocol biopsy. We phenotyped their adoptively transferred and peripherally circulating Treg compartments using CITEseq and investigated the focal lymphocytic infiltrates with spatial proteomic and transcriptomic technologies. FINDINGS: Graft survival rates were not significantly different between Treg-treated patients and the control reference group. None of the Treg-treated patients experienced clinical rejection episodes or developed de novo donor-specific antibodies, and three of ten successfully reduced their immunosuppression to tacrolimus monotherapy. All Treg-treated patients who underwent a protocol biopsy nine months post-transplantation exhibited focal lymphocytic infiltrates. Spatial profiling analysis revealed a prominent CD20+ B cell signature within cell therapy-associated immune infiltrates, distinct from the pro-inflammatory myeloid signature typically associated with the rejection biopsies. A regulatory gene expression program (IKZF2, IL10, PD-L1, TIGIT) characterized the cell therapy-associated immune infiltrates at a transcriptional level. CONCLUSIONS: We demonstrate for the first time that immune cell infiltrates in transplanted kidneys can occur following adoptive Treg cell therapy in humans, potentially facilitating within-graft T:B cell interactions that promote local immune regulation. FUNDING: 7th EU Framework Programme, Grant/Award Number: 260687; National Institute for Health Research (NIHR).
2024-11-14 | GSE281542 | GEO
Project description:Treponema pallidum subspecies pallidum (T. pallidum) infection induces significant immune responses, resulting in tissue damage. Gene expression plays an essential role in regulating the progression of syphilis infection. However, little is known about the regulatory role of miRNAs in the immune response to T. pallidum infection. Here, we analyze the differential expression of miRNAs in peripheral blood mononuclear cells (PBMCs) between secondary syphilis (SS) patients and healthy controls and study the correlation between miRNAs expression and clinical features with bioinformatics.
2020-08-19 | GSE156421 | GEO
Project description:Associations of immune cell homing gene signatures and infiltrates of lymphocyte subsets in human melanomas: discordance with CD163+ myeloid cell infiltrates
| PRJNA752356 | ENA
Project description:The Atlas of Immune Infiltrates in Islet Cell Allo-transplantation
| PRJNA817208 | ENA
Project description:Previous observations have demonstrated that the agricultural fungicide vinclozolin and the pesticide DDT (dichlorodiphenyltrichloroethane) induce transgenerational sperm epimutations involving DNA methylation. These two environmental toxicants were used to investigate the impacts of parent-of-origin outcross on the epigenetic transgenerational inheritance of disease. Male and female rats were collected from a paternal outcross (POC) or a maternal outcross (MOC) F4 generation control and exposure lineages for pathology and epigenetic analysis. This model allows the parental allelic transmission of disease and epimutations to be investigated. There was increased pathology incidence in MOC outcross F4 generation male prostate, kidney, obesity and multiple diseases through a maternal allelic transmission. The POC outcross F4 generation female offspring had increase pathology incidence for kidney, obesity and multiple diseases through the paternal allelic transmission. Some disease such as testis or ovarian pathology appear to be transmitted through the combined actions of both male and female alleles. Analysis of the F4 generation sperm epigenomes identified differential DNA methylated regions (DMRs) in a genome-wide analysis. Observations demonstrate that DDT and vinclozolin have the potential to promote the epigenetic transgenerational inheritance of disease and sperm epimutations to the outcross F4 generation in a sex specific and exposure specific manner.
2019-07-23 | GSE130258 | GEO
Project description:Background: Immune cells in the tumor microenvironment have prognostic value. In preclinical models, recruitment and infiltration of these cells depends on immune cell homing (ICH) genes such as chemokines, cell adhesion molecules, and integrins. We hypothesized ICH ligands CXCL9-11 and CCL2-5 would be associated with intratumoral T-cells, while CXCL13 would be more associated with B-cell infiltrates. Methods: Samples of human melanoma were submitted for gene expression analysis and immune cells identified by immunohistochemistry. Associations between the two were evaluated with unsupervised hierarchical clustering using correlation matrices from Spearman rank tests. Univariate analysis performed Mann-Whitney tests. Results: For 119 melanoma specimens, analysis of 78 ICH genes revealed association among genes with nonspecific increase of multiple immune cell subsets: CD45+, CD8+ and CD4+ T-cells, CD20+ B-cells, CD138+ plasma cells, and CD56+ NK-cells. ICH genes most associated with these infiltrates included ITGB2, ITGAL, CCL19, CXCL13, plus receptor/ligand pairs CXCL9 and CXCL10 with CXCR3; CCL4 and CCL5 with CCR5. This top ICH gene expression signature was also associated with genes representing immune-activation and effector function. In contrast, CD163+ M2-macrophages was weakly associated with a different ICH gene signature. Conclusion: These data do not support our hypothesis that each immune cell subset is uniquely associated with specific ICH genes. Instead, a larger set of ICH genes identifies melanomas with concordant infiltration of B-cell and T-cell lineages, while CD163+ M2-macrophage infiltration suggesting alternate mechanisms for their recruitment. Future studies should explore the extent ICH gene signature contributes to tertiary lymphoid structures or cross-talk between homing pathways.
2021-08-07 | GSE181525 | GEO
Project description:To further investigate the pathogenesis of syphilis with diabetes, we used a gene chip expression profile from a rabbit model of syphilis with diabetes as a discovery platform to identify potential genes. Grouped into normal control group (n=2) and syphilis combined with diabetes group (n=3).
2020-05-06 | GSE135053 | GEO