Persistent pneumococcal colonisation in anti-retroviral-treated HIV infection is associated with nasal inflammation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE296893 | GEO | 2025/11/03
REPOSITORIES: GEO
Similar Datasets
Project description:Persistent pneumococcal colonisation in anti-retroviral-treated HIV infection is associated with nasal inflammation
| PRJNA1261889 | ENA
Project description:Immune activation in people living with HIV on anti-retroviral therapy is associated with increased risk of morbidity and mortality, but the underlying mechanisms are poorly understood. To identify whether perturbation of immunological pathways persist at systems level, we compared genome-wide whole blood transcriptomes from 26 people living with HIV on long-term anti-retroviral therapy with 12 HIV-negative healthy controls. All participants were Caucasian male adults recruited from London, UK. People living with HIV were on anti-retroviral therapy for a median of 8.5 years (interquartile range 3-16 years). They had undetectable plasma HIV viral load (<40 copies/ml) and median circulating CD4 counts of 703 cells/µl (interquartile range 491-841 cells/µl).
2021-02-26 | E-MTAB-8891 | biostudies-arrayexpress
Project description:Purpose: Influenza virus infections affect millions of people annually. Current available vaccines provide varying rates of protection. There is a knowledge gap on how the nasal microbiota, particularly established pneumococcal colonization, shapes the response to influenza vaccination. Methods: In this study, we inoculated healthy adults with live S. pneumoniae and vaccinated them three days later with either TIV or LAIV. Vaccine-induced immune responses were assessed in nose, blood and lung. Results: Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, pre-existing pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared to either TIV or an unvaccinated group. Conclusions: These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae. This important confounder should be considered when assessing LAIV efficacy.
2021-03-10 | GSE164649 | GEO
Project description:Background: Post-COVID syndrome (PCS) currently affects approximately 3-17% of people following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has the potential to become a significant global health burden. While PCS exhibits diverse symptoms, improved assessment methods are being developed to guide therapy. Despite this, there is a lack of mechanistic insights and treatment options. Objective: To elucidate molecular mechanisms underlying PCS by employing single-cell RNA transcriptomics on patients’ nasal tissue and in vitro validation. Methods: Single-cell RNA transcriptomic analysis was conducted on nasal biopsies from 25 PCS patients with moderate or severe PCS symptoms. Identification of cell types, signaling, and cell-cell communication was performed. In vitro, air-liquid interface cultures were employed to validate findings, with a particular focus on the TNFα-TGFβ axis. Results: Severe PCS was associated with reduced numbers of ciliated cells, increased immune cell presence, and inflammatory signaling leading to TGFβ and TNFα upregulation, all without any viral load. This induced an epithelial-mesenchymal transition, increasing basal cell abundance and a mis-stratified nasal epithelium. In vitro experiments validated TGFβ and TNFα as causal cytokines promoting the reduced abundance of ciliated epithelium and expansion of basal epithelial cells. As such, we posit that a sustained severe PCS phenotype was not linked to continued viral load but instead to immune cell presence and persistent cytokine production. Conclusions: Our study reveals a pathway for persistent severe PCS involving immune-mediated nasal tissue damage, suggesting therapeutic potential by targeting the TNFα-TGFβ axis. The restoration of the nasal epithelium may prove to be a possible treatment strategy for PCS, akin to interventions in other chronic inflammatory conditions.
2025-06-16 | GSE299529 | GEO
Project description:The nasal and bronchial epithelium are unified parts of the respiratory tract that are affected in the monogenic disorder cystic fibrosis (CF). Recent studies have uncovered that nasal and bronchial tissues exhibit intrinsic variability, including differences in mucociliary cell composition and expression of unique transcriptional regulatory proteins which relate to germ layer origin. In the present study, we explored transcriptomic differences between cultured nasal and bronchial epithelial cells from people with CF. Comparison of air-liquid interface-differentiated epithelial cells from subjects with CF revealed distinct mucociliary differentiation states of nasal and bronchial cultures. Moreover, using RNA sequencing we identified cell type-specific signature transcription factors in differentiated nasal and bronchial epithelial cells.
2023-11-21 | GSE241801 | GEO
Project description:Objectives: To determine whether disease processes related to granulomatosis with polyangiitis (GPA) are reflected in gene expression profiles of nasal mucosa. Methods: Nasal brushings of the inferior turbinate were obtained from 32 patients with GPA (10 with active nasal disease, 13 with prior nasal disease, 9 with no history of nasal disease) and a composite comparator group with and without inflammatory nasal disease (12 healthy people, 15 with sarcoidosis, 8 with allergic rhinitis). Differential gene expression was assessed between subgroups of GPA and comparators. Results: 339 genes were differentially expressed between the GPA and comparator groups (absolute fold change > 1.5; false discovery rate < 0.05). Top canonical pathways upregulated in nasal brushings from patients with GPA include granulocyte adhesion and diapedesis (p=8.6 E-22), agranulocyte adhesion and diapedesis (p=1.3 E-14), interleukin 10 signaling (3.0 E-11), and TREM1 signaling (9.0 E-11). A set of genes differentially expressed in GPA independent of nasal disease activity status included genes related to epithelial barrier integrity (fibronectin 1, desmosomal proteins) and several matricellular proteins (e.g. osteonectin, osteopontin). Significant overlap of differentially expressed genes was observed between active and prior nasal disease GPA subgroups. Peripheral blood neutrophil and mononuclear gene expression levels associated with GPA were similarly altered in the nasal gene expression profiles of patients with active or prior nasal disease. Conclusions: Profiling the nasal transcriptome in GPA reveals gene expression signatures related to innate immunity, inflammatory cell chemotaxis, extracellular matrix composition, and epithelial barrier integrity. Airway-based expression profiling is feasible and informative in GPA.
2018-08-29 | GSE119136 | GEO
Project description:The nasal epithelium represents the first line of defense against inhaled pathogens, allergens, and irritants and plays a key role in the pathogenesis of a spectrum of acute and chronic airways diseases. Despite age-dependent clinical phenotypes triggered by these noxious stimuli, little is known about how ageing affects the structure and function of the airway epithelium that is crucial for lung homeostasis and host defense. The aim of this study was therefore to determine age-related differences in structural and functional properties of primary nasal epithelial cultures from healthy children and non-smoking elderly people. To achieve this goal, highly differentiated nasal epithelial cultures were established from nasal brushes at air-liquid-interface and used to study epithelial cell type composition, mucin (MUC5AC and MUC5B) expression and ion transport properties. Further, we determined age-dependent molecular signatures using global proteomic analysis. We found lower numeric densities of ciliated cells and higher levels of MUC5AC expression in cultures from children vs. elderly people. Bioelectric studies showed no differences in basal ion transport properties, ENaC-mediated sodium absorption or CFTR-mediated chloride transport, but detected decreased calcium-activated TMEM16A-mediated chloride secretory responses in cultures from children vs. elderly people. Proteome analysis identified distinct age-dependent molecular signatures associated with ciliation and mucin biosynthesis, as well as other pathways implicated in ageing. Our data identified intrinsic, age-related differences in structure and function of the nasal epithelium and provide a basis for further studies on the role of these findings in age-dependent airways disease phenotypes observed with a spectrum of respiratory infections and other noxious stimuli.
2022-02-28 | PXD030130 | Pride
Project description:Chronic liver disease is becoming a leading cause of illness and mortality in people living with human immunodeficiency virus (HIV) (PLWH) undergoing suppressive anti-retroviral therapy. Its main etiology has been reported to be coinfection with hepatitis B (HBV) and C (HCV) viruses. Accumulating evidence indicate chronic liver inflammation and fibrosis can potentially lead to the development of hepatocellular carcinoma (HCC). Therefore, monitoring of the disease progression in PLWH is required. The present study aimed to explore the plasma protein profiles of patients with HIV infection and those coinfected with HBV and HCV using shotgun proteomics.
2024-06-29 | PXD053504 | JPOST Repository
Project description:Streptococcus pneumoniae colonization in the upper respiratory tract is linked to pneumococcal disease development, predominantly affecting young children and older adults. As the global population ages and comorbidities increase, there is a heightened concern about this infection. We investigated the immunological responses of older adults to pneumococcal controlled human infection by analysing the cellular composition and gene expression in the nasal mucosa. Our comparative analysis with data from a concurrent study in younger adults revealed distinct gene expression patterns in older individuals susceptible to colonization, highlighted by neutrophil activation and elevated levels of CXCL9 and CXCL10. Unlike younger adults challenged with pneumococcus, older adults did not show recruitment of monocytes into the nasal mucosa following nasal colonization. However, older adults who were protected from colonization showed increased degranulation of CD8+ T cells, both before and after pneumococcal challenge. These findings suggest age-associated cellular changes, in particular enhanced mucosal inflammation, that may predispose older adults to pneumococcal colonization.
2024-07-12 | GSE261277 | GEO
Project description:Blood RNA sequencing in HIV-negative healthy volunteers and people living with HIV on effective, long-term anti-retroviral therapy
| PRJEB37238 | ENA