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Published in: BMC Immunology 1/2003

Open Access 01-12-2003 | Research article

Genetic control of the innate immune response

Authors: Christine A Wells, Timothy Ravasi, Geoffrey J Faulkner, Piero Carninci, Yasushi Okazaki, Yoshihide Hayashizaki, Matthew Sweet, Brandon J Wainwright, David A Hume

Published in: BMC Immunology | Issue 1/2003

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Abstract

Background

Susceptibility to infectious diseases is directed, in part, by the interaction between the invading pathogen and host macrophages. This study examines the influence of genetic background on host-pathogen interactions, by assessing the transcriptional responses of macrophages from five inbred mouse strains to lipopolysaccharide (LPS), a major determinant of responses to gram-negative microorganisms.

Results

The mouse strains examined varied greatly in the number, amplitude and rate of induction of genes expressed in response to LPS. The response was attenuated in the C3H/HeJlps d strain, which has a mutation in the LPS receptor Toll-like receptor 4 (TLR4). Variation between mouse strains allowed clustering into early (C57Bl/6J and DBA/2J) and delayed (BALB/c and C3H/ARC) transcriptional phenotypes. There was no clear correlation between gene induction patterns and variation at the Bcg locus (Slc11A1) or propensity to bias Th1 versus Th2 T cell activation responses.

Conclusion

Macrophages from each strain responded to LPS with unique gene expression profiles. The variation apparent between genetic backgrounds provides insights into the breadth of possible inflammatory responses, and paradoxically, this divergence was used to identify a common transcriptional program that responds to TLR4 signalling, irrespective of genetic background. Our data indicates that many additional genetic loci control the nature and the extent of transcriptional responses promoted by a single pathogen-associated molecular pattern (PAMP), such as LPS.
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Metadata
Title
Genetic control of the innate immune response
Authors
Christine A Wells
Timothy Ravasi
Geoffrey J Faulkner
Piero Carninci
Yasushi Okazaki
Yoshihide Hayashizaki
Matthew Sweet
Brandon J Wainwright
David A Hume
Publication date
01-12-2003
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2003
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/1471-2172-4-5

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