Genetic control of the innate immune response

被引：107

作者：

Christine A Wells

Timothy Ravasi

Geoffrey J Faulkner

Piero Carninci

Yasushi Okazaki

Yoshihide Hayashizaki

Matthew Sweet

Brandon J Wainwright

David A Hume

机构：

[1] Institute for Molecular Biosciences, The University of Queensland, Brisbane

[2] Lab. for Genome Explor. Res. Group, Genomic Sciences Centre, Riken Yokohama Institute

来源：

BMC Immunology | / 4卷 / 1期

关键词：

Mouse Strain; Arginase; Transcriptional Program; Inbred Mouse Strain; Autocrine Factor;

D O I：

10.1186/1471-2172-4-5

中图分类号：

学科分类号：

摘要：

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/HeJlpsd 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. © 2003 Wells et al; licensee BioMed Central Ltd.

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