Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15667717_1.fastq.gz | Fastqsanger.gz | |||
| SRR15667717_2.fastq.gz | Fastqsanger.gz | |||
| SRR15667718_1.fastq.gz | Fastqsanger.gz | |||
| SRR15667718_2.fastq.gz | Fastqsanger.gz | |||
| SRR15667719_1.fastq.gz | Fastqsanger.gz |
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Project description:The amount of SARS-CoV-2 detected in the upper respiratory tract (URT viral load) is a key driver of transmission of infection. Current evidence suggests that mechanisms constraining URT viral load are different from those controlling lower respiratory tract viral load and disease severity. Understanding such mechanisms may help to develop treatments and vaccine strategies to reduce transmission. Combining mathematical modelling of URT viral load dynamics with transcriptome analyses we aimed to identify mechanisms controlling URT viral load. COVID-19 patients were recruited in Spain during the first wave of the pandemic. RNA sequencing of peripheral blood and targeted NanoString nCounter transcriptome analysis of nasal epithelium were performed and gene expression analysed in relation to paired URT viral load samples collected within 15 days of symptom onset. Proportions of major immune cells in blood were estimated from transcriptional data using computational differential estimation. Weighted correlation network analysis (adjusted for cell proportions) and fixed transcriptional repertoire analysis were used to identify associations with URT viral load, quantified as standard deviations (z-scores) from an expected trajectory over time.
2023-04-01 | E-MTAB-12791 | biostudies-arrayexpress
Project description:Acute respiratory infections (ARI), which generally begin with colonization of the mucosal surfaces of the upper respiratory tract (URT), are a leading cause of morbidity and mortality with the highest rate in infants. As a common colonizer of the URT, and one of the most prevalent causes of life-threatening infections in the pediatric population, Streptococcus pneumoniae (Spn) was used as a model pathogen to investigate the effect of age during URT infection. We used RNA-sequencing to transcriptionally profile and compare the mucosal epithelia of infant and adult mice at baseline (mock-infected) and during Spn infection. Analysis of the screen revealed an age-dependent alteration of genes involved in mucosal defense mechanisms that included dampened expression of ubiquitous antimicrobial molecules and tight junction proteins in infant mice compared to adults. These results demonstrate a window of vulnerability during postnatal development when altered mucosal barrier function may facilitate bacterial colonization and invasion.
2018-10-16 | GSE116604 | GEO
Project description:The nasal mucosa is the first immunologically active site that respiratory viruses encounter and establishing immunity at the initial point of pathogen contact is essential for preventing viral spread. Influenza A virus (IAV) in humans preferentially replicates in the upper respiratory tract (URT) but mouse models of infection result in lower respiratory tract (LRT) infection. Here we optimize IAV inoculation to enhance replication in the nasal turbinate (NT) and study local B cell immunity. We demonstrate that URT-targeted IAV infection stimulates robust local B cell responses, including germinal centre (GC) B cell formation in the NT, outside of classical nasal associated lymphoid tissues (NALT). NT GC contribute to local tissue resident B cell generation and enhance local antibody production. Furthermore, URT-focused immunization also induces significant GC formation in the NT. Finally, we detect steady-state GC in the NT of both mice and healthy humans, suggesting continuous immune surveillance triggered by environmental stimuli. These findings highlight the pivotal role of the NT in local and systemic immunity, with important implications for future mucosal vaccines targeting the upper airways.
2025-03-06 | GSE289606 | GEO
Project description:<p><strong>Background</strong>: Influenza A virus (IAV) causes a wide spectrum of clinical outcomes, from mild symptoms to life-threatening pneumonia. Recent studies have highlighted the role of the upper respiratory tract (URT) microbiota in modulating immune responses and influencing disease severity, yet the underlying mechanisms remain poorly understood.</p><p><strong>Purpose</strong>: To investigate how the URT microbiota and host metabolic profiles differ between mild and severe influenza A cases, and to elucidate potential microbiota–metabolome interactions contributing to disease pathogenesis.</p><p><strong>Methods</strong>: We enrolled 392 adult patients with laboratory-confirmed IAV between October 2022 and December 2023. Pharyngeal swabs and blood samples were collected for microbiome and metabolome profiling. URT microbiota was assessed via 16S ribosomal RNA (16S rRNA) and metagenomic sequencing, while plasma metabolites were profiled using untargeted metabolomics.</p><p><strong>Results</strong>: Among 392 age- and sex-matched patients (196 mild, 196 severe), the severe group exhibited significantly higher white blood cell (WBC), neutrophil (NEU), platelet (PLT), and high-sensitivity C-reactive protein (hs-CRP) levels. Microbiome analysis revealed greater α-diversity (Observed Features, Chao1, ACE) in severe cases, while β-diversity remained comparable. 16S rRNA and metagenomic sequencing showed high concordance at the genus level, with metagenomics providing improved species-level resolution. Linear discriminant analysis effect size (LEfSe) identified enrichment of pathogenic taxa including Parvimonas micra and Veillonella parvula, as well as inflammation-associated pathways in severe cases, whereas mild cases harbored taxa and metabolic functions potentially associated with host defense. Metabolomic profiling revealed 122 differential plasma metabolites; anti-inflammatory and antioxidant metabolites were enriched in mild cases, whereas lipid biosynthesis and glycosylation-related metabolites were significantly enriched in severe cases. Microbial diversity and specific taxa abundances correlated with immune markers, supporting microbiota–host immune interactions in disease severity.</p><p><strong>Conclusion</strong>: This study reveals distinct compositional and functional alterations in the URT microbiota between mild and severe IAV cases. Severe cases are characterized by higher microbial richness and pro-inflammatory microbial functions, whereas mild cases exhibit protective metabolic signatures. These findings underscore the potential of targeting the microbiota–metabolome axis in predicting influenza severity and developing novel host–microbiome-based therapies.</p>
2025-11-03 | MTBLS13112 | MetaboLights