Progression of whole blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in patients with severe influenza
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PROVIDER: PRJNA436726 | ENA |
REPOSITORIES: ENA
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Project description:Transcriptional profiles are increasingly used to investigate the severity, subtype and pathogenesis of disease. We now describe whole blood RNA signatures and local and systemic immune mediator levels in a large cohort of adults hospitalised with influenza from which extensive clinical and investigational data was obtained. Signatures reflecting interferon-related antiviral pathways were common up to day 4 of symptoms in cases not requiring mechanical ventilatory support; in those needing mechanical ventilation, an inflammatory, activated neutrophil and cell stress/death (‘bacterial’) pattern was seen, even early after disease onset. Identifiable bacterial co-infection was not necessary for this ‘bacterial’ signature but could enhance its development while attenuating the early ‘viral’ signature. Our findings emphasise the importance of timing and severity in the interpretation of transcriptomic profiles and soluble mediator levels, and identify specific patterns of immune activation that may enable the development of novel diagnostics and therapeutics
2018-03-03 | GSE111368 | GEO
Project description:Transcriptional profiles and host-response biomarkers are used increasingly to investigate the severity, subtype and pathogenesis of disease. We now describe whole-blood mRNA signatures and concentrations of local and systemic immunological mediators in 131 adults hospitalized with influenza, from whom extensive clinical and investigational data were obtained by MOSAIC investigators. Signatures reflective of interferon-related antiviral pathways were common up to day 4 of symptoms in patients who did not require mechanical ventilator support; in those who needed mechanical ventilation, an inflammatory, activated-neutrophil and cell-stress or death ('bacterial') pattern was seen, even early in disease. Identifiable bacterial co-infection was not necessary for this 'bacterial' signature but was able to enhance its development while attenuating the early 'viral' signature. Our findings emphasize the importance of timing and severity in the interpretation of host responses to acute viral infection and identify specific patterns of immune-system activation that might enable the development of novel diagnostic and therapeutic tools for severe influenza.
| S-EPMC5985949 | biostudies-literature
Project description:While critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during COVID-19 ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using scRNA-seq and plasma proteomics, we discovered that compared to bacterial ARDS, COVID-19 was associated with expansion of distinct neutrophil states characterized by interferon (IFN) and prostaglandin (PG) signalling. Dexamethasone during severe COVID-19 depleted circulating neutrophils, altered IFNactive neutrophils, downregulated interferon-stimulated gene, and activated IL1R2+ve neutrophils. Dexamethasone also expanded immunosuppressive immature neutrophils and remodeled cellular interactions by changing neutrophils from information receivers into information providers. Male patients had higher proportions of IFNactive neutrophils, preferential steroid-induced immature neutrophil expansion, and possibly different effects on outcome. Our single-cell atlas (www.biernaskielab.ca/COVID_neutrophil) defines COVID-19-enriched neutrophil states and molecular mechanisms of dexamethasone action to develop targeted immunotherapies for severe COVID-19.
2021-10-05 | GSE157789 | GEO
Project description:Epidemics of influenza virus are of great challenges to the public concern. The lung inflammation and injury caused by excessive inflammatory cell infiltration into the lungs and overproduction of inflammatory mediators are major consequences during influenza virus infection. Neutrophils are vital for anti-microbial defense. However, the roles of neutrophils during viral infections are less clear. Furthermore, the molecular regulation of neutrophil fate and function at the viral infected sites is largely elusive. We found that BCL6 deficiency in neutrophils, but not in monocytes nor lung macrophages, attenuated host inflammation and morbidity following influenza infection. Mechanistically, BCL6 bound to the neutrophil gene loci involved in cellular apoptosis specifically at the site of infection. As such, BCL6 disruption resulted in increased expression of apoptotic genes in neutrophils in the respiratory tract, but not in the circulation nor bone marrow. Consequently, BCL6 deficiency promoted tissue neutrophil apoptosis. Our results have revealed a previously unappreciated role of BCL6 in modulating neutrophil apoptosis at the site of infection for the regulation of host disease development following viral infection.
2019-06-24 | GSE126622 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE39199: Gene Expression Response to Interferon Treatment at 12h and 24 in A549 cells GSE39200: The NS1 protein of influenza A virus suppresses interferon-regulated activation of antigen-presentation and immune-proteasome pathways Refer to individual Series
2012-07-09 | E-GEOD-39202 | biostudies-arrayexpress
Project description:A BALB/c mouse model of severe influenza A/H1N1 infection was constructed, and whole-transcriptome sequencing of mice treated with PD-1 checkpoint blockade before severe A/PR8(H1N1) influenza infection and IgG2a isotype control before infection were performed.
2022-01-06 | GSE192915 | GEO
Project description:A BALB/c mouse model of severe influenza A/H1N1 infection was constructed, and whole-transcriptome sequencing of mice treated with PD-1 checkpoint blockade before severe A/PR8(H1N1) influenza infection and IgG2a isotype control before infection were performed.
2022-01-06 | GSE192914 | GEO
Project description:Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection. We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized to NanoString mRNA probes, counts normalized, and analyzed using linear models controlling for age and bacterial co-infections (FDR q<0.05). Comparing pediatric samples collected near admission, children with Prolonged MODS for ≥7 days (n=38; 9 deaths) had significant upregulation of nine mRNA transcripts associated with neutrophil degranulation (RETN, TCN1, OLFM4, MMP8, LCN2, BPI, LTF, S100A12, GUSB) compared to those who recovered more rapidly from MODS (n=27). These neutrophil transcripts present in early samples predicted Prolonged MODS or death when compared to patients who recovered, however in paired longitudinal samples, they were not differentially expressed over time. Instead, five genes involved in protein metabolism and/or adaptive immunity signaling pathways (RPL3, MRPL3, HLA-DMB, EEF1G, CD8A) were associated with MODS recovery within a week. Thus, early increased expression of neutrophil degranulation genes indicated worse clinical outcomes in children with influenza infection, consistent with reports in adult cohorts with influenza, sepsis, and acute respiratory distress syndrome.
2023-07-07 | GSE236877 | GEO
Project description:Introduction Epidemiological studies have shown that smoking is associated with increased incidence of severe viral infections leading to hospitalisation. Moreover, studies in experimental models have identified impaired antiviral responses and altered inflammatory responses, yet it is unclear which immune cells are involved and whether this varies over the course of infection. Methods To test how cigarette smoking affects the response to influenza viral infection over time, female BALB/c mice were exposed to cigarette smoke or air twice a day for 24-28 days and infected with H3N2 influenza or mock infection on day 21. Three and seven days after infection, changes in immune cell populations, and mRNA expression/viral clearance in lung tissue were analysed. Results Smoke-exposed mice lost significantly more weight than air-exposed controls after influenza infection, indicating that smoking resulted in more severe disease. Immune cell and lung tissue transcriptome analysis revealed that neutrophil infiltration was prolonged and macrophage activation dysregulated after infection in smoke-exposed mice compared to air-exposed controls. Expression of genes in IL-6 and interferon pathways was similarly longer active. In parallel, we observed lower clearance of viral RNA in smoke-exposed mice after infection compared to air-exposed controls, indicating ineffective antiviral responses. Adaptive immune responses were unchanged in infected smoking animals compared to nonsmoking mice. Conclusion Altogether, the data from our mouse model indicate that cigarette smoke exposure prolongs innate immune responses against influenza. The results from this study help to explain the susceptibility of current smokers to severe influenza disease.
2024-06-21 | GSE269227 | GEO
Project description:BPIFA1 Regulates Interferon-Mediated Lung Neutrophil Recruitment During Acute Inflammation
| PRJNA412049 | ENA