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The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remain unknown. Here, we show that access of Bacillus Calmette-Guérin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell expansion and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, BCG-educated HSCs generate epigenetically modified macrophages that provide significantly better protection against virulent M. tuberculosis infection than naïve macrophages. By using parabiotic and chimeric mice, as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCG-induced HSC reprogramming is sustainable in vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.
Pubmed ID: 29328912 RIS Download
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Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.
View all literature mentionsJava toolset for working with next generation sequencing data in the BAM format.
View all literature mentionsSoftware package for high-performance read alignment, quantification and mutation discovery.General purpose read aligner which can be used to map both genomic DNA-seq reads and RNA-seq reads. Subread aligner as fast, accurate and scalable read mapping by seed-and-vote.These programs were also implemented in Bioconductor R package Rsubread.
View all literature mentionsSoftware for aligning sequencing reads against large reference genome. Consists of three algorithms: BWA-backtrack, BWA-SW and BWA-MEM. First for sequence reads up to 100bp, and other two for longer sequences ranged from 70bp to 1Mbp.
View all literature mentionsSoftware tool to automate quality and adapter trimming as well as quality control, with some added functionality to remove biased methylation positions for RRBS sequence files for directional, non-directional or paired-end sequencing. Wrapper around Cutadapt and FastQC to consistently apply adapter and quality trimming to FastQ files, with extra functionality for Reduced Representation Bisulfite Sequencing data.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsSoftware package for low-level analyses of single-cell RNA-seq data. Used for quality control, data exploration and normalization, cell cycle phase assignment, identification of highly variable and correlated genes, clustering into subpopulations and marker gene detection.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsThis monoclonal targets Mouse CCR2 Fluorescein MAb (Clone 475301)
View all literature mentionsThis monoclonal targets CD3
View all literature mentionsThis monoclonal targets CD115 (c-fms)
View all literature mentionsThis monoclonal targets Mouse CD44
View all literature mentionsThis monoclonal targets CD127
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD3e
View all literature mentionsThis monoclonal targets Mouse CCR2 Phycoerythrin MAb (Clone 475301)
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets Siglec-F
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis monoclonal targets Ly-6G
View all literature mentionsThis monoclonal targets Ly-6C
View all literature mentionsThis monoclonal targets Ly-6C
View all literature mentionsThis monoclonal targets F4/80
View all literature mentionsThis monoclonal targets CD34
View all literature mentionsThis monoclonal targets CD135 (FLT3)
View all literature mentionsThis monoclonal targets CD48
View all literature mentionsThis monoclonal targets CD150
View all literature mentionsThis monoclonal targets Ly-6A/E (Sca-1)
View all literature mentionsThis monoclonal targets CD117 (c-Kit)
View all literature mentionsThis unknown targets Biotin
View all literature mentionsThis monoclonal targets Ly-6G and Ly-6C
View all literature mentionsThis monoclonal targets CD45R / B220
View all literature mentionsThis monoclonal targets CD8a
View all literature mentionsThis monoclonal targets CD4
View all literature mentionsThis monoclonal targets CD5
View all literature mentionsThis monoclonal targets CD11b
View all literature mentionsThis monoclonal targets TER-119/Erythroid cells
View all literature mentionsThis monoclonal targets CD16/CD32
View all literature mentionsMus musculus with name B6.129S7-Ifngr1tm1Agt/J from IMSR.
View all literature mentionsMus musculus with name B6.129S4-Ccr2tm1Ifc/J from IMSR.
View all literature mentions
Mus musculus with name B6.SJL-Ptprca Pepc
Mus musculus with name NOD.129S7(B6)-Rag1tm1Mom/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsStatistical 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 mentionsSoftware tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.
View all literature mentionsA suite of software tools for analyzing and manipulating next-generation sequencing datasets, such as FASTQ, BED and BAM format files. These tools provide a stable and modular platform for data management and analysis.
View all literature mentionsA software tool which provides interactive visualization capability for the integrated analysis of high-dimensional gene expression data.
View all literature mentionsA Cytoscape plug-in that visualizes the non-redundant biological terms for large clusters of genes in a functionally grouped network. It can be used in combination with GOlorize. The identifiers can be uploaded from a text file or interactively from a network of Cytoscape. The type of identifiers supported can be easily extended by the user. ClueGO performs single cluster analysis and comparison of clusters. From the ontology sources used, the terms are selected by different filter criteria. The related terms which share similar associated genes can be combined to reduce redundancy. The ClueGO network is created with kappa statistics and reflects the relationships between the terms based on the similarity of their associated genes. On the network, the node colour can be switched between functional groups and clusters distribution. ClueGO charts are underlying the specificity and the common aspects of the biological role. The significance of the terms and groups is automatically calculated. ClueGO is easy updatable with the newest files from Gene Ontology and KEGG. Platform: Windows compatible, Mac OS X compatible, Linux compatible, Unix compatible
View all literature mentionsBioconductor software package for Empirical analysis of Digital Gene Expression data in R. Used for differential expression analysis of RNA-seq and digital gene expression data with biological replication.
View all literature mentionsA Bioconductor package that can import gates defined by the commercial package FlowJo and work with them in a manner consistent with the other flow packages in Bioconductor. FlowJo is a commercial GUI based software package from TreeStar Inc. for the visualization and analysis of flow cytometry data. One of the FlowJo standard export file types is the FlowJo Workspace. This is an XML document that describes files and manipulations that have been performed in the FlowJo GUI environment. This package can take apart the FlowJo workspace and deliver the data into R in the flowCore paradigm.
View all literature mentionsA collection of tools for flow cytometer and application setup, data acquisition, and data analysis that help streamline flow cytometry workflows. It provides features to help users integrate flow systems into new application areas, including index sorting for stem cell and single-cell applications, as well as automation protocols for high-throughput and robotic laboratories.
View all literature mentionsStatistical 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
Mus musculus with name B6.SJL-Ptprca Pepc
Mus musculus with name B6.129S7-Ifngr1tm1Agt/J from IMSR.
View all literature mentionsMus musculus with name B6.129S4-Ccr2tm1Ifc/J from IMSR.
View all literature mentionsMus musculus with name NOD.129S7(B6)-Rag1tm1Mom/J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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