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Interferon-λ Mediates Non-redundant Front-Line Antiviral Protection against Influenza Virus Infection without Compromising Host Fitness.

Immunity | 2017

Lambda interferons (IFNλs) or type III IFNs share homology, expression patterns, signaling cascades, and antiviral functions with type I IFNs. This has complicated the unwinding of their unique non-redundant roles. Through the systematic study of influenza virus infection in mice, we herein show that IFNλs are the first IFNs produced that act at the epithelial barrier to suppress initial viral spread without activating inflammation. If infection progresses, type I IFNs come into play to enhance viral resistance and induce pro-inflammatory responses essential for confronting infection but causing immunopathology. Central to this are neutrophils which respond to both cytokines to upregulate antimicrobial functions but exhibit pro-inflammatory activation only to type I IFNs. Accordingly, Ifnlr1-/- mice display enhanced type I IFN production, neutrophilia, lung injury, and lethality, while therapeutic administration of PEG-IFNλ potently suppresses these effects. IFNλs therefore constitute the front line of antiviral defense in the lung without compromising host fitness.

Pubmed ID: 28514692 RIS Download

Research resources used in this publication

Antibodies used in this publication

Associated grants

None

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


GraphPad Prism (tool)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

View all literature mentions

Gene Expression Omnibus (GEO) (tool)

RRID:SCR_007303

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

View all literature mentions

SAM format (tool)

RRID:SCR_012093

A generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.

View all literature mentions

DESeq2 (tool)

RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

View all literature mentions

Gene Expression Omnibus (GEO) (tool)

RRID:SCR_005012

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

View all literature mentions

Anti-GFP antibody (antibody)

RRID:AB_300798

This polyclonal targets GFP

View all literature mentions

PE anti-mouse CD24 (antibody)

RRID:AB_10578416

This monoclonal targets CD24

View all literature mentions

Anti-Prosurfactant Protein C (proSP-C) Antibody (antibody)

RRID:AB_91588

This polyclonal targets Prosurfactant Protein C

View all literature mentions

PE anti-mouse Siglec H (antibody)

RRID:AB_2189147

This monoclonal targets Siglec H

View all literature mentions

PE anti-mouse I-A/I-E (antibody)

RRID:AB_313323

This monoclonal targets I-A/I-E

View all literature mentions

APC/Cyanine7 anti-mouse Ly-6G (antibody)

RRID:AB_10640819

This monoclonal targets Ly-6G

View all literature mentions

PE anti-mouse Ly-6G/Ly-6C (Gr-1) (antibody)

RRID:AB_313373

This monoclonal targets Ly-6G Ly-6C

View all literature mentions

PE/Cyanine7 anti-mouse CD11c (antibody)

RRID:AB_493568

This monoclonal targets CD11c

View all literature mentions

APC anti-mouse/human CD11b (antibody)

RRID:AB_312795

This monoclonal targets CD11b

View all literature mentions

PE/Cyanine7 anti-mouse CD3epsilon (antibody)

RRID:AB_312685

This monoclonal targets CD3epsilon

View all literature mentions

InVivoPlus anti-mouse Ly6G (antibody)

RRID:AB_1107721

This monoclonal targets Ly6G

View all literature mentions

Leukocyte Common Antigen (antibody)

RRID:AB_2174426

This monoclonal targets Mouse Thymus / Spleen The 30-F11 clone has been reported to react with all isoforms and both alloantigens of CD45, which is found on hematopoietic stem cells and all cells of hematopoietic origin, except erythrocytes.

View all literature mentions

B6.129S2-Ifnar1tm1Agt/Mmjax (organism)

RRID:MMRRC_032045-JAX

Mus musculus with name B6.129S2-Ifnar1tm1Agt/Mmjax from MMRRC.

View all literature mentions

TM4 Microarray Software Suite - TIGR MultiExperiment Viewer (software toolkit)

RRID:SCR_001915

A desktop application for the analysis, visualization and data-mining of large-scale genomic data. It is a versatile microarray tool, incorporating sophisticated algorithms for clustering, visualization, classification, statistical analysis and biological theme discovery. MeV generates informative and interrelated displays of expression and annotation data from single or multiple experiments. A huge array of alrogithms are included in MeV modules, and are available at a button-click, such as K-means clustering, Hierarchical clustering, t-Tests, Significance Analysis of Microarrays, Gene Set Enrichment Analysis, and EASE. Extensive documentation is available for helping new users get started with MeV. A Quickstart Guide provides the tutorial a brand new person will need to get their first dataset loaded and displayed in the program. Returning MEV users will want to check out the release notes to see what new features are available in the latest versions of the program. Tutorials have been written about several of its more involved features.

View all literature mentions

CRAN (software repository)

RRID:SCR_003005

Network of ftp and web servers around world that store identical, up to date, versions of code and documentation for R. Package archive network for R programming language.

View all literature mentions

HTSeq (software resource)

RRID:SCR_005514

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Software Python package that provides infrastructure to process data from high-throughput sequencing assays. While the main purpose of HTSeq is to allow you to write your own analysis scripts, customized to your needs, there are also a couple of stand-alone scripts for common tasks that can be used without any Python knowledge.

View all literature mentions

SAMTOOLS (software resource)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

View all literature mentions

Bowtie (software resource)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

View all literature mentions

TopHat (software resource)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

View all literature mentions

cutadapt (software resource)

RRID:SCR_011841

Software tool that removes adapter sequences from DNA sequencing reads.

View all literature mentions

FastQC (software resource)

RRID:SCR_014583

Quality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.

View all literature mentions

B6.129(Cg)-Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J (organism)

RRID:IMSR_JAX:007676

Mus musculus with name B6.129(Cg)-Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J from IMSR.

View all literature mentions

B6.Cg-Tg(S100A8-cre.-EGFP)1Ilw/J (organism)

RRID:IMSR_JAX:021614

Mus musculus with name B6.Cg-Tg(S100A8-cre.-EGFP)1Ilw/J from IMSR.

View all literature mentions

C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions

CRAN (software repository)

RRID:SCR_003005

Network of ftp and web servers around world that store identical, up to date, versions of code and documentation for R. Package archive network for R programming language.

View all literature mentions

TM4 Microarray Software Suite - TIGR MultiExperiment Viewer (software toolkit)

RRID:SCR_001915

A desktop application for the analysis, visualization and data-mining of large-scale genomic data. It is a versatile microarray tool, incorporating sophisticated algorithms for clustering, visualization, classification, statistical analysis and biological theme discovery. MeV generates informative and interrelated displays of expression and annotation data from single or multiple experiments. A huge array of alrogithms are included in MeV modules, and are available at a button-click, such as K-means clustering, Hierarchical clustering, t-Tests, Significance Analysis of Microarrays, Gene Set Enrichment Analysis, and EASE. Extensive documentation is available for helping new users get started with MeV. A Quickstart Guide provides the tutorial a brand new person will need to get their first dataset loaded and displayed in the program. Returning MEV users will want to check out the release notes to see what new features are available in the latest versions of the program. Tutorials have been written about several of its more involved features.

View all literature mentions

HTSeq (software resource)

RRID:SCR_005514

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Software Python package that provides infrastructure to process data from high-throughput sequencing assays. While the main purpose of HTSeq is to allow you to write your own analysis scripts, customized to your needs, there are also a couple of stand-alone scripts for common tasks that can be used without any Python knowledge.

View all literature mentions

SAMTOOLS (software resource)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

View all literature mentions

Bowtie (software resource)

RRID:SCR_005476

Software ultrafast memory efficient tool for aligning sequencing reads. Bowtie is short read aligner.

View all literature mentions

TopHat (software resource)

RRID:SCR_013035

Software tool for fast and high throughput alignment of shotgun cDNA sequencing reads generated by transcriptomics technologies. Fast splice junction mapper for RNA-Seq reads. Aligns RNA-Seq reads to mammalian-sized genomes using ultra high-throughput short read aligner Bowtie, and then analyzes mapping results to identify splice junctions between exons.TopHat2 is accurate alignment of transcriptomes in presence of insertions, deletions and gene fusions.

View all literature mentions

cutadapt (software resource)

RRID:SCR_011841

Software tool that removes adapter sequences from DNA sequencing reads.

View all literature mentions

FastQC (software resource)

RRID:SCR_014583

Quality control software that perform checks on raw sequence data coming from high throughput sequencing pipelines. This software also provides a modular set of analyses which can give a quick impression of the quality of the data prior to further analysis.

View all literature mentions

B6.129(Cg)-Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J (organism)

RRID:IMSR_JAX:007676

Mus musculus with name B6.129(Cg)-Gt(ROSA)26Sortm4(ACTB-tdTomato.-EGFP)Luo/J from IMSR.

View all literature mentions

B6.Cg-Tg(S100A8-cre.-EGFP)1Ilw/J (organism)

RRID:IMSR_JAX:021614

Mus musculus with name B6.Cg-Tg(S100A8-cre.-EGFP)1Ilw/J from IMSR.

View all literature mentions

C57BL/6J (organism)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

View all literature mentions

PE anti-mouse Siglec H (antibody)

RRID:AB_2189147

This monoclonal targets Siglec H

View all literature mentions

PE anti-mouse I-A/I-E (antibody)

RRID:AB_313323

This monoclonal targets I-A/I-E

View all literature mentions

APC/Cyanine7 anti-mouse Ly-6G (antibody)

RRID:AB_10640819

This monoclonal targets Ly-6G

View all literature mentions

PE anti-mouse Ly-6G/Ly-6C (Gr-1) (antibody)

RRID:AB_313373

This monoclonal targets Ly-6G Ly-6C

View all literature mentions

PE anti-mouse CD24 (antibody)

RRID:AB_10578416

This monoclonal targets CD24

View all literature mentions

PE/Cyanine7 anti-mouse CD11c (antibody)

RRID:AB_493568

This monoclonal targets CD11c

View all literature mentions

APC anti-mouse/human CD11b (antibody)

RRID:AB_312795

This monoclonal targets CD11b

View all literature mentions

PE/Cyanine7 anti-mouse CD3epsilon (antibody)

RRID:AB_312685

This monoclonal targets CD3epsilon

View all literature mentions

Anti-Prosurfactant Protein C (proSP-C) Antibody (antibody)

RRID:AB_91588

This polyclonal targets Prosurfactant Protein C

View all literature mentions

InVivoPlus anti-mouse Ly6G (antibody)

RRID:AB_1107721

This monoclonal targets Ly6G

View all literature mentions

Anti-GFP antibody (antibody)

RRID:AB_300798

This polyclonal targets GFP

View all literature mentions

Leukocyte Common Antigen (antibody)

RRID:AB_2174426

This monoclonal targets Mouse Thymus / Spleen The 30-F11 clone has been reported to react with all isoforms and both alloantigens of CD45, which is found on hematopoietic stem cells and all cells of hematopoietic origin, except erythrocytes.

View all literature mentions

Anti-Prosurfactant Protein C (proSP-C) Antibody (antibody)

RRID:AB_91588

This polyclonal targets Prosurfactant Protein C

View all literature mentions

Anti-Prosurfactant Protein C (proSP-C) Antibody (antibody)

RRID:AB_91588

This polyclonal targets Prosurfactant Protein C

View all literature mentions

PE anti-mouse CD24 (antibody)

RRID:AB_10578416

This monoclonal targets CD24

View all literature mentions

Anti-GFP antibody (antibody)

RRID:AB_300798

This polyclonal targets GFP

View all literature mentions