Key Points
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We have re-analysed and compared microarray data from 32 published studies and uncovered a common host-transcriptional-response to pathogens.
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Sub-clusters of functionally-related genes are preferentially induced by different host cell types.
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Toll-like receptors (TLRs) are responsible for both common and pathogen-specific programmes of gene expression.
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Some pathogens actively repress portions of the host transcriptional response and such activities can be correlated with pathogen virulence and disease severity.
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The use of material from the clinic and from animal models provides information about the dynamics of infection and its resolution in vivo.
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Gene expression profiling of pathogen-associated cancers provides clues about the mechanisms of tumorigenesis.
Abstract
DNA microarrays have allowed us to monitor the effects of pathogens on host-cell gene expression programmes in great depth and on a broad scale. The comparison of results that have been generated by these studies is complex, and such a comparison has not previously been attempted in a systematic manner. In this review, we have collated and compared published transcriptional-profiling data from 32 studies that involved 77 different host–pathogen interactions, and have defined a common host-transcriptional-response. We outline gene expression patterns in the context of Toll-like receptor and pathogen-mediated signalling pathways, and summarize the contributions that transcriptional-profiling studies have made to our understanding of the infectious disease process.
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Acknowledgements
The authors thank E. Herbolsheimer and G. Bell for help with data processing and Gene Ontology annotation. We apologize to any authors whose papers we inadvertently missed when compiling Supplementary information S1,S2,S3 (tables and references). This work was funded by the National Institute of Allergy and Infectious Diseases.
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DATABASES
Swiss-Prot
FURTHER INFORMATION
Glossary
- DNA MICROARRAY
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An ordered array of DNA probes of known sequence on a solid support, fabricated on a very small scale. The probes are used to interrogate the composition of DNA mixtures through hybridization.
- INTERFERON
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(IFN). Cytokines that can induce cells to resist infection. Type 1 IFNs (α and β) are produced by several cell types; type 2 IFN(γ) is produced by T cells and NK cells.
- TRANSCRIPTOME
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The set of mRNA transcripts that are present in any one cell at a given time.
- CLUSTER ANALYSIS
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A multivariate statistical classification technique that partitions variables (which for microarray data are genes or samples) into groups (clusters) based on shared characteristics (in this case, gene expression patterns).
- LATENT INFECTION (LATENCY)
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The stage of some virus life-cycles in which no progeny virions are produced. Viral gene expression is restricted.
- APOPTOSIS
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Programmed cell death, a controlled physiological process by which a cell terminates its own existence.
- ADAPTOR PROTEINS
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Linker proteins that connect cell-surface receptors to downstream members of intracellular signalling pathways.
- T-HELPER (TH) CELLS
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T cells that help in the activation of other cell types; TH1 cells are mainly involved in macrophage activation, TH2 cells in B-cell activation.
- FORWARD GENETICS
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The experimental process of identifying the genes responsible for a defined function or phenotype.
- REVERSE GENETICS
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The experimental process of assigning functions to a gene, usually through mutation or inhibition of its expression.
- GRAM-POSITIVE BACTERIA
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A group of bacteria that retain the stain of Gram's solution after rinsing. They have a single cell wall that does not contain LPS. Gram-negative bacteria have a double cell wall that contains LPS, which prevents the retention of the stain.
- DOUBLE-STRANDED (ds)RNA
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Double-stranded RNA, which is produced during the life-cycle of many viruses but which is otherwise not normally found in the cell (except for very short RNA species).
- GLIOMA CELL LINE
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A self-propagating cell population that is derived from a cancer of glial cells.
- ELISA
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Enzyme-linked immunosorbent assay — an assay in which antigen is detected by an antibody linked to an enzyme that produces a coloured product.
- VIRULENCE FACTOR
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A pathogen protein that is essential for causing disease in a host.
- RNA INTERFERENCE
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(RNAI) Post-transcriptional gene silencing (PTGS) induced by the direct introduction of dsRNA.
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Jenner, R., Young, R. Insights into host responses against pathogens from transcriptional profiling. Nat Rev Microbiol 3, 281–294 (2005). https://doi.org/10.1038/nrmicro1126
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DOI: https://doi.org/10.1038/nrmicro1126
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