Dual spatial host-bacterial gene expression in Mycobacterium abscessus respiratory infections DOI Creative Commons
Federico Di Marco, Francesca De Nicola, Francesca Giannese

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Oct. 9, 2024

Co-localization of spatial transcriptome information host and pathogen can revolutionize our understanding microbial pathogenesis. Here, we aimed to demonstrate that customized bacterial probes be successfully used identify host-pathogen interactions in formalin-fixed-paraffin-embedded (FFPE) tissues by probe-based transcriptomics technology. We analyzed the gene expression transcripts with transcriptomic profile murine lung tissue chronically infected Mycobacterium abscessus embedded agar beads. Customized mycobacterial were designed for constitutively expressed rpoB (an RNA polymerase β subunit) virulence factor precursor lsr2, modulated oxidative stress. found a correlation between expression, abundance airways, an increased lsr2 high Overall, potential dual assay FFPE tissues, paving way simultaneous detection transcriptomes pathological tissues.

Language: Английский

Human vascularized macrophage-islet organoids to model immune-mediated pancreatic β cell pyroptosis upon viral infection DOI Creative Commons
Liuliu Yang, Yuling Han, Tuo Zhang

et al.

Cell stem cell, Journal Year: 2024, Volume and Issue: 31(11), P. 1612 - 1629.e8

Published: Sept. 3, 2024

There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation proinflammatory macrophages. Single-cell RNA sequencing (scRNA-seq) analysis islets exposed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coxsackievirus B4 (CVB4) viruses identified activation macrophages and β pyroptosis. To distinguish viral versus proinflammatory-macrophage-mediated pyroptosis, developed pluripotent stem (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression function both cells endothelial compared with separately cultured cells. Notably, within induced Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement This established hPSC-derived as valuable tool for studying immune-cell-mediated damage uncovered mechanism during exposure.

Language: Английский

Citations

8
Discrete placental gene expression signatures accompany diabetic disease classifications during pregnancy DOI Creative Commons
Enrico R. Barrozo, Diana Racusin, Michael D. Jochum

et al.

American Journal of Obstetrics and Gynecology, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Language: Английский

Citations

4
The placental transcriptomic profile determined by maternal COVID-19 disease encompasses alterations reminiscent of preeclampsia DOI
Ana Medel-Martínez, Mark Strunk, Alberto Cebollada

et al.

Placenta, Journal Year: 2025, Volume and Issue: 165, P. 127 - 135

Published: Feb. 28, 2025

Language: Английский

Citations

0
Incorporating machine learning and statistical methods to address maternal healthcare disparities in US: A systematic review DOI

Hala Al Sliti,

Nada A. Rasheed, Saumya Tripathi

et al.

International Journal of Medical Informatics, Journal Year: 2025, Volume and Issue: unknown, P. 105918 - 105918

Published: April 1, 2025

Language: Английский

Citations

0
Single-nucleus transcriptional profiling of the placenta reveals the syncytiotrophoblast stress response to COVID-19 DOI Creative Commons
Rachel A. Keuls, Scott A. Ochsner, Mary B. O’Neill

et al.

American Journal of Obstetrics and Gynecology, Journal Year: 2025, Volume and Issue: 232(4), P. S160 - S175.e7

Published: April 1, 2025

COVID-19 in pregnancy is associated with placental immune activation, inflammation, and vascular malperfusion, but its impact on syncytiotrophoblast biology function unclear. This study aimed to determine the effects of maternal syncytiotrophoblasts using single-nucleus transcriptional profiling compare stress responses preeclampsia. For characterization syncytiotrophoblasts, we used RNA sequencing platform, single-cell combinatorial indexing (sci-RNA-seq3), profile villi fetal membranes from unvaccinated patients symptomatic at birth (n = 4), gestational age-matched controls a case critical second trimester delivery term 1). Clustering nuclei differential gene expression analysis was performed Seurat. Gene ontology conducted Enrichr. High-confidence target identify key transcription factor nodes governing response SARS-CoV-2 infection. Bioinformatic approaches were further dataset published preeclampsia signatures. Tissue analysis, including immunofluorescence, validate data histology for an expanded cohort placentas: 6), asymptomatic 3), 5), severe features 7). The analyzed comprised 15 cell clusters 47,889 nuclei. We identified 3 representing fusing mature overlapping distinct COVID-19. analyses indicated that following alterations syncytiotrophoblasts: (1) endoplasmic reticulum activation signaling pathways, unfolded protein integrated response; (2) regulation by CCAAT/enhancer-binding beta (CEBPB), master lineage; (3) upregulation preeclampsia-associated genes. Using complementary methods, confirmed increased levels proteins (eg, BiP, G3BP1) (spliced XBP1 mRNA), CEBPB (phosphorylation) Increased cytotrophoblast proliferation (Ki-67) also detected COVID-19, consistent trophoblast injury. Markers demonstrated similarities phenotype Maternal lineage factor, CEBPB. Similarities between provide insights into their clinical association.

Language: Английский

Citations

0
A survey of SARS-CoV-2 tropism DOI Creative Commons

Xiangxing Jin,

Xiang Ren, Xianwen Ren

et al.

Infectious Diseases & Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Abstract The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome 2 (SARS-CoV-2), has significantly burdened global public health. However, the tropism of SARS-CoV-2 within human body remains not fully understood. In this review, we overview literature on infection across various organs and tissues. We summarize relevant specimen types, techniques for examining tropism, findings at both organ/tissue cellular levels. To systematically evaluate evidence supporting tissue establish a hierarchical classification system based two key criteria: (1) origin (2) detection methodology. Clinical specimens obtained directly from COVID-19 patients provide most definitive evidence, whereas organoid-derived animal models indicate potential infectivity under artificial conditions. terms methods, prioritize viral particle identification over protein or RNA detection, as latter requires further confirmation to productive infection. Our that potentially targets multiple organ systems, including tract, lungs, kidneys, heart, blood vessels, pancreas, small intestine, liver, salivary glands. By contrast, central nervous reproductive uncertain validation. At level, identify specific target cell types vulnerable infection, ciliated epithelial cells, alveolar type II pneumocytes, enterocytes, cardiomyocytes, vascular endothelial renal tubular pancreatic acinar cells. Furthermore, analyze correlation between angiotensin-converting enzyme receptor distribution patterns well variations in specificity among different variants. expect review comprehensive landscape enhance our understanding life cycle consequences body.

Language: Английский

Citations

0
Maternal SARS-CoV-2 infection in pregnancy disrupts gene expression in Hofbauer cells with limited impact on cytotrophoblasts DOI Creative Commons
Elizabeth Ann L. Enninga, Huy Quang Quach, Jin Sung Jang

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(2), P. e1011990 - e1011990

Published: Feb. 7, 2024

Background Hofbauer cells (HBCs) and cytotrophoblasts (CTBs) are major cell populations in placenta. The indirect impact of maternal SARS-CoV-2 disease on these that not directly infected has been extensively studied. Herein, we profiled gene expression HBCs CTBs isolated from placentae recovered pregnant subjects with during all trimesters pregnancy, active infection, vaccinated subjects, those who were unexposed to the virus. Methods Placentae collected within 4 h post-delivery membrane-free tissues enzymatically digested for isolation CTBs. RNA extracted sequenced using 150bp paired-end reads. Differentially expressed genes (DEGs) identified by DESeq2 package R enriched GO Biological Processes, KEGG Pathway, Reactome Gene Sets, Hallmark Canonical Pathways. Protein-protein interactions among DEGs modelled STRING BioGrid. Results Pregnant (n = 30) recruited categorized into six groups: i) first (1T, n 4), ii) second (2T, 5), iii) third (3T, 5) trimester, iv) tested positive at delivery (Delivery, v) never (Control, 6), vi) fully mRNA-vaccinated (Vaccinated, 5). Compared Control group, analysis showed had significantly altered profiles, 2T group having highest number (1,696), followed 3T 1T groups (1,656 958 DEGs, respectively). These pathways involved immune regulation host defense, including production cytokines, chemokines, antimicrobial proteins, ribosomal assembly, neutrophil degranulation inflammation, morphogenesis, migration/adhesion. interaction mapped oxidative phosphorylation, translation, extracellular matrix organization, type I interferon signaling. Only 95, 23, 8 1T, 2T, groups, respectively. Similarly, 11 3 Reassuringly, mRNA vaccination did induce an inflammatory response placental cells. Conclusions Our studies demonstrate a significant infection inner mesenchymal HBCs, limited effect lining CTB SARS-CoV-2. associated identify potential targets therapeutic intervention.

Language: Английский

Citations

3
Maternal-fetal cytokine profiles in acute SARS-CoV-2 “breakthrough” infection after COVID-19 vaccination DOI Creative Commons
Claire H. Packer,

Olyvia Jasset,

Nikolina Hanniford

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 8, 2025

Vaccination is protective against severe COVID-19 disease, yet whether vaccination reduces COVID-19-associated inflammation in pregnancy has not been established. The objective of this study to characterize maternal and cord cytokine profiles acute SARS-CoV-2 "breakthrough" infection (BTI) after vaccination, compared with unvaccinated uninfected controls. 66 pregnant individuals enrolled the MGH biorepository (March 2020-April 2022) were included. Maternal sera collected from 26 21 vaccinated infection. Cord at delivery. 19 term dyads without current or prior analyzed as Cytokines quantified using Human Inflammation 20-Plex ProcartaPlex assay. There was a significantly higher incidence severe/critical illness (10/26 (38%) vs. 0/21 (0%), p<0.01). Significantly levels TNFα CD62P observed BTI (p<0.05). Network correlation analyses revealed distinct response vs individuals. Neither nor resulted elevated cytokines Multivariate demonstrate setting associated during infection, which may reflect vaccine-mediated priming immune system. A fetal inflammatory specific observed.

Language: Английский

Citations

0
Fetal MAVS and type I IFN signaling pathways control ZIKV infection in the placenta and maternal decidua DOI Creative Commons
Yael Alippe, Leran Wang, Reyan Coskun

et al.

The Journal of Experimental Medicine, Journal Year: 2024, Volume and Issue: 221(9)

Published: July 23, 2024

The contribution of placental immune responses to congenital Zika virus (ZIKV) syndrome remains poorly understood. Here, we leveraged a mouse model ZIKV infection identify mechanisms innate restriction exclusively in the fetal compartment placenta. principally infected mononuclear trophoblasts junctional zone, which was limited by mitochondrial antiviral-signaling protein (MAVS) and type I interferon (IFN) signaling mechanisms. Single nuclear RNA sequencing revealed MAVS-dependent expression IFN-stimulated genes (ISGs) spongiotrophoblasts but not other cells that use alternate pathways induce ISGs. Ifnar1-/- or Mavs-/- placentas associated with greater adjacent immunocompetent decidua, heterozygous Mavs+/- Ifnar1+/- dams carrying immunodeficient fetuses sustained maternal viremia tissue than wild-type fetuses. Thus, MAVS-IFN fetus restricts zone trophoblasts, modulates dissemination outcome for both pregnant mother.

Language: Английский

Citations

2
Transplacental Transmission of SARS-CoV-2: A Narrative Review DOI Creative Commons
Minh Tien Bui, Cam Anh Nguyen Le, Khanh Linh Duong

et al.

Medicina, Journal Year: 2024, Volume and Issue: 60(9), P. 1517 - 1517

Published: Sept. 18, 2024

The study aims to explore the potential for transplacental transmission of SARS-CoV-2, focusing on its pathophysiology, placental defense mechanisms, and clinical implications maternal neonatal health.

Language: Английский

Citations

2