Inflammation induced by influenza virus impairs innate control of human pneumococcal carriage
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ABSTRACT:
PROVIDER: PRJNA482564 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7586320_1.fastq.gz | Fastqsanger.gz | |||
| SRR7586320_2.fastq.gz | Fastqsanger.gz | |||
| SRR7586330_1.fastq.gz | Fastqsanger.gz | |||
| SRR7586330_2.fastq.gz | Fastqsanger.gz | |||
| SRR7586340_1.fastq.gz | Fastqsanger.gz |
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Project description:Secondary bacterial pneumonia following influenza infection is a significant cause of mortality worldwide. Upper respiratory tract pneumococcal carriage is important as both determinants of disease and population transmission. The immunological mechanisms that contain pneumococcal carriage are well-studied in mice but remain unclear in humans. Loss of this control of carriage following influenza infection is associated with secondary bacterial pneumonia during seasonal and pandemic outbreaks. We used a human type 6B pneumococcal challenge model to show that carriage acquisition induces early degranulation of resident neutrophils and recruitment of monocytes to the nose. Monocyte function associated with clearance of pneumococcal carriage. Prior nasal infection with live attenuated influenza virus induced inflammation, impaired innate function and altered genome-wide nasal gene responses to pneumococcal carriage. Levels of the cytokine IP-10 promoted by viral infection at the time of pneumococcal encounter was positively associated with bacterial density. These findings provide novel insights in nasal immunity to pneumococcus and viral-bacterial interactions during co-infection.
2018-07-25 | GSE117580 | GEO
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:Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes. Here, we demonstrate that the viral hemagglutinin (HA) mediates bacterial OM by inducing a pro-inflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings show that it is the inflammatory response that mediates pneumococcal replication; not viral suppression of the immune system or epithelial damage. This study provide the first evidence that HA induced inflammation drives pneumococcal replication in the middle ear cavity, which has important consequences to the treatment of pneumococcal OM.
2013-01-01 | GSE41098 | GEO
Project description:Pneumococcal colonization impairs nasal and lung mucosal immune responses to Live Attenuated Influenza Vaccination in adults
| PRJNA692462 | ENA
Project description:Influenza A virus (IAV) predisposes individuals to secondary infections with the bacterium Streptococcus pneumoniae (the pneumococcus). Infections may manifest as pneumonia, sepsis, meningitis or otitis media (OM). It remains controversial as to whether secondary pneumococcal disease is due to the induction of an aberrant immune response or IAV induced immunosuppression. Moreover, as the majority of studies have been performed in the context of pneumococcal pneumonia, it remains unclear how far these findings can be extrapolated to other pneumococcal disease phenotypes. Here, we demonstrate that the viral hemagglutinin (HA) mediates bacterial OM by inducing a pro-inflammatory response in the middle ear cavity in a replication-dependent manner. Importantly, our findings show that it is the inflammatory response that mediates pneumococcal replication; not viral suppression of the immune system or epithelial damage. This study provide the first evidence that HA induced inflammation drives pneumococcal replication in the middle ear cavity, which has important consequences to the treatment of pneumococcal OM. Five-day old C57BL/6 mice were colonised intranasally (i.n.) with 2M-CM-^W103 colony forming units (CFU) of S. pneumoniae EF3030Lux in 3 M-BM-5Ls of PBS. Alternatively, mice were mock-infected with an equivalent volume of phosphate buffered saline (PBS). At 14-days of age, infant mice were infected i.n. with 20 plaque forming units (PFU) (PR8/34, Cambridge/34 and WSN/33) or 102.5 PFU (all other virus strains) of egg-grown IAV in 3 M-BM-5Ls of PBS. Viral doses were selected to ensure a reproducible infection with minimum morbidity and no mortality. Six days post-IAV infection, mice were euthanised and organs were collected for analysis. Six independent biological replicates (where both ears from one mouse were pooled to create one sample) were used for each condition and analyzed using the NimbleGen platform (12M-CM-^W135K Mouse Gene Expression Arrays, Roche Nimblegen, USA). Indirect labeling, hybridization and washing was performed according to the manufacturerM-bM-^@M-^Ys instructions. Array images were acquired with a NimbleGen MS200 scanner, and images were processed with NimbleScan software using the RMA algorithm. Data was processed using Arraystar (DNASTAR, USA) with default settings as described in the manual. Differential expression tests were performed with a moderated T-test implemented in Arraystar, followed by FDR correction of the P values (Q-values) according to the method of Storey and Tibshirani
2013-01-01 | E-GEOD-41098 | biostudies-arrayexpress
Project description:Background: We employed DNA microarray technology to investigate the host response to Streptococcus pneumoniae in a mouse model of asymptomatic carriage. Over a period of six weeks, we profiled transcript abundance and complexity in the Nasal Associated Lymphoid Tissue (NALT) to identify genes whose expression differed between pneumococcal-colonized and uncolonized states. Results: Colonization with S. pneumoniae altered the expression of hundreds of genes over the course of the study, demonstrating that carriage is a dynamic process characterized by increased expression of a set of early inflammatory responses, including induction of a Type 1 Interferon response, and the production of several antimicrobial factors. Subsequent to this initial inflammatory response, we observed increases in transcripts associated with T cell development and activation, as well as wounding, basement membrane remodeling, and cell proliferation. Our analysis suggests that microbial colonization induced expression of genes encoding components critical for controlling JAK/STAT signaling, including stat1, stat2, socs3, and mapk1, as well as induction of several Type 1 Interferon-inducible genes and other antimicrobial factors at the earliest stages of colonization. Conclusions: Examining multiple time points over six weeks of colonization demonstrated that asymptomatic carriage stimulates a dynamic host response characterized by temporal waves with distinct biological programs. Our data suggest that the usual response to the presence of the pneumocccus is an initial controlled inflammatory response followed by activation of host physiological processes such as response to wounding, basement membrane remodeling, and increasing cellular numbers that ultimately allow the host to maintain an intact epithelium and eventually mount a preventive adaptive immune response. A disease state experiment design type is where the state of some disease such as infection, pathology, syndrome, etc is studied.
2009-08-31 | GSE16803 | GEO
Project description:The objective of this study is to: 1) Characterize the immune responsiveness to administration of non-live vaccines in three cohorts of healthy adult subjects through the analysis of blood leukocytes transcriptional profiles. 2) Validate whole blood transcriptional profiles generated from standard 3mL blood draws versus 200uL blood draws obtained by finger stick. 3) Discover potential biomarkers for immune-responsiveness to non-live vaccines. A total of 621 blood samples were collected either by venipuncture (387) or finger prick (234) from four groups of healthy adults receiving either, 2009/10 seasonal influenza or 23-valent pneumococcal vaccine or placebo (saline) injections. Subjects were recruited in 3 cohorts with 4-7 individuals per group; cohort 3 was recruited for validation of the systemic day 1 immune signature in response to seasonal influenza and pneumococcal vaccination. From each subject, peripheral blood was drawn into Tempus tubes (Applied Biosystems) or obtained by finger prick into micro capillaries and then transferred into tempus reagent to lyse blood cells and stabilize RNA before storing at -80ºC until mRNA extraction. The training set for transcriptional profiling of blood obtained by venipuncture was performed in cohort 1 which included 6 healthy adult individuals receiving seasonal influenza vaccine, 6 healthy adult individuals receiving pneumococcal vaccine, and 6 healthy adult individuals receiving placebo (saline injections). The test set for transcriptional profiling of blood obtained by venipuncture was performed in cohort 2 which included 6 healthy adult individuals receiving seasonal influenza vaccine, 6 healthy adult individuals receiving pneumococcal vaccine, and 6 healthy adult individuals receiving placebo (saline injections). The validation set for confirming systemic day 1 transcriptome immune signature in response to seasonal influenza and pneumococcal vaccination was performed in cohort 3 which included 6 healthy adult individuals receiving seasonal influenza vaccine and 4 healthy adult individuals receiving pneumococcal vaccine. The training set for transcriptional profiling of blood obtained by finger prick was performed in cohort 2 and the test set in cohort 1.
2013-04-19 | E-GEOD-30101 | biostudies-arrayexpress
Project description:The objective of this study is to: 1) Characterize the immune responsiveness to administration of non-live vaccines in three cohorts of healthy adult subjects through the analysis of blood leukocytes transcriptional profiles. 2) Validate whole blood transcriptional profiles generated from standard 3mL blood draws versus 200uL blood draws obtained by finger stick. 3) Discover potential biomarkers for immune-responsiveness to non-live vaccines. A total of 621 blood samples were collected either by venipuncture (387) or finger prick (234) from four groups of healthy adults receiving either, 2009/10 seasonal influenza or 23-valent pneumococcal vaccine or placebo (saline) injections. Subjects were recruited in 3 cohorts with 4-7 individuals per group; cohort 3 was recruited for validation of the systemic day 1 immune signature in response to seasonal influenza and pneumococcal vaccination. From each subject, peripheral blood was drawn into Tempus tubes (Applied Biosystems) or obtained by finger prick into micro capillaries and then transferred into tempus reagent to lyse blood cells and stabilize RNA before storing at -80ºC until mRNA extraction. The training set for transcriptional profiling of blood obtained by venipuncture was performed in cohort 1 which included 6 healthy adult individuals receiving seasonal influenza vaccine, 6 healthy adult individuals receiving pneumococcal vaccine, and 6 healthy adult individuals receiving placebo (saline injections). The test set for transcriptional profiling of blood obtained by venipuncture was performed in cohort 2 which included 6 healthy adult individuals receiving seasonal influenza vaccine, 6 healthy adult individuals receiving pneumococcal vaccine, and 6 healthy adult individuals receiving placebo (saline injections). The validation set for confirming systemic day 1 transcriptome immune signature in response to seasonal influenza and pneumococcal vaccination was performed in cohort 3 which included 6 healthy adult individuals receiving seasonal influenza vaccine and 4 healthy adult individuals receiving pneumococcal vaccine. The training set for transcriptional profiling of blood obtained by finger prick was performed in cohort 2 and the test set in cohort 1.
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Project description:The objective of this study is to: 1) Characterize the cellular origin of transciptional signatures observed on day 1 after vaccination with 2009/10 seasonal influenza and pneumococcal vaccine discovered by transcriptional profiling of whole blood samples in data set “WholeBlood_SysVax”. 2) Discover potential biomarkers for immune-responsiveness to non-live vaccines. In this Series, a total of 72 samples of leukocyte subsets (neutrophils, monocytes, CD4+ T and CD8+ T lymphocytes) were isolated before and 24 hours after vaccination from 6 healthy adult individuals receiving seasonal influenza and 4 healthy adult individuals receiving pneumococcal vaccine. From each subject, neutrophils and peripheral blood mononuclear cells were obtained by Ficoll gradient separation and then CD14+ monocytes, CD4+ T and CD8+ T cells were purified by sequential positive bead selection. Cells were transferred into RLT buffer and stored at -80ºC until mRNA extraction.
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