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Mice, microbes and models of infection

Nature Reviews Genetics volume 4, pages 195–205 (2003)Cite this article

Key Points

  • The immune systems of mice and humans are similar and they can often be challenged with the same, or similar, pathogens.

  • Most mouse mutants with a defective immune system have a broad vulnerability to infection.

  • Forward genetic studies led to the discovery of genes determining resistance or susceptibility to bacterial infection (a recent example is the cloning of the Naip5/Birc1e gene).

  • Targeted gene knockout approaches have been successfully used to dissect the molecular pathways that are involved in host defence.

  • The complexities of bacterial gene expression during mammalian infection cannot be addressed by in vitro experiments alone. The concerted effort of host and pathogen gene-expression profiling by microarray technology and mouse genetics will be the method of choice for in vivo-induced gene analysis in the future.

  • For many human infectious diseases we do not have suitable animal models available; in the next few years it will be necessary to systematically develop new mouse models for infectious diseases.

Abstract

We urgently need animal models to study infectious disease. Mice are susceptible to a similar range of microbial infections as humans. Marked differences between inbred strains of mice in their response to pathogen infection can be exploited to analyse the genetic basis of infections. In addition, the genetic tools that are available in the laboratory mouse, and new techniques to monitor the expression of bacterial genes in vivo, make it the principal experimental animal model for studying mechanisms of infection and immunity.

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Figure 1: Toll-like receptor (TLR4) signalling.
Figure 2: The infected host — a complex and dynamic environment.
Figure 3: In vivo expression technology approaches.

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Acknowledgements

The authors thank M. Probst-Kepper for stimulating discussions, M. Rohde, K. E. J. Dittmar and S. Weiss for the figure on the infected host, and J. Lauber, D. Bruder and R. Geffers for help in preparing the manuscript. J.B. would like to thank D. Bitter-Suermann, J. Wehland and H. von Boehmer for ongoing support and encouragement. The authors are supported by the Deutsche Forschungsgemeinschaft and the German Federal Ministry of Education and Research.

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  1. German Research Centre for Biotechnology (GBF), Mascheroder Weg 1, Braunschweig, D-38124, Germany

    Jan Buer & Rudi Balling

  2. Institute of Medical Microbiology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany

    Jan Buer

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Correspondence to Rudi Balling.

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Databases

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Birc1e

Cd14

IFN-γ

IFNGR1

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IL-4

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Lgn1

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TNF-α

Tnfrp55

Tnfrp75

Toll

FURTHER INFORMATION

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Phenome project

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World Health Report 2002

Glossary

MACROPHAGES

Phagocytic cells that respond to non-self material by releasing substances that stimulate other cells of the immune system and are involved in antigen presentation.

PHAGOLYSOSOME

An organelle in a phagocytic cell that is formed by fusion of an ingested particle with a lysosome containing hydrolytic enzymes that digest the particle.

LYMPHOCYTES

Antigen-specific cells of the immune system.

OPSONIZATION

The process by which factors of the immune-serum coat bacteria and, therefore, enhance phagocytosis.

COMPLEMENT

A large group of interacting plasma proteins that act together to attack extracellular pathogens.

HELMINTHS

A collective term for parasitic worms, including flukes, tapeworms and roundworms.

FACULTATIVE PARASITE

A parasite that is able to survive away from its host.

PHAGOSOME

A membrane-bound vesicle that contains microbes or particulate material from the extracellular environment.

LIPOPOLYSACCHARIDE

(LPS). A complex glycolipid found on the surface of Gram-negative bacteria that is a powerful inflammatory stimulus.

CYTOKINES

A group of proteins that form a dynamic network of intercellular messenger molecules that regulate various aspects of physiology, including the immune response to infection.

GRANULOMA

A site of chronic inflammation that is usually triggered by persistent infectious agents, such as mycobacteria.

NAIVE T CELL

A cell that has not yet encountered antigen.

ENTEROCOLITIS

Inflammation of the small intestine and the colon.

SIGNATURE-TAGGED MUTAGENESIS

A technique for detecting genes that are required for survival and growth in vivo that uses modified transposons to allow high-throughput screening of randomly generated mutants.

DIFFERENTIAL DISPLAY

A technique for detecting those genes that are expressed only under specific conditions; it involves isolation and comparison of mRNA from two or more populations.

DNA MICROARRAYS

An array of PCR products or oligonucleotides (corresponding to either genomic or cDNA sequences) deposited on solid glass slides that can be used to identify patterns of gene expression.

AUXOTROPHIC MUTATION

A mutation that affects the ability of an organism to make a particular molecule that is essential for growth.

FLUORESCENCE-ACTIVATED CELL SORTING

(FACS). A method in which dissociated and individual living-cells are sorted, in a liquid stream, according to the intensity of fluorescence that they emit as they pass through a laser beam.

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Buer, J., Balling, R. Mice, microbes and models of infection. Nat Rev Genet 4, 195–205 (2003). https://doi.org/10.1038/nrg1019

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