%0 Journal Article
%T Genetic control of the innate immune response
%A Christine A Wells
%A Timothy Ravasi
%A Geoffrey J Faulkner
%A Piero Carninci
%A Yasushi Okazaki
%A Yoshihide Hayashizaki
%A Matthew Sweet
%A Brandon J Wainwright
%A David A Hume
%J BMC Immunology
%D 2003
%I BioMed Central
%R 10.1186/1471-2172-4-5
%X 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.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.Susceptibility to infection is determined by the nature of the pathogen, and by the fitness of an individual to respond appropriately. The nature of the host response is controlled in part by the appropriate recognition of PAMPs by cells of the innate immune system [1,2]. Ineffective PAMP recognition, or an inappropriate response underlies clinical complications such as circulating bacterial load or septic shock. Lipopolysaccharide (LPS), a component of bacterial cell walls, is the predominant trigger of adverse clinical consequences of infection with gram-negative bacteria, including host procoagulant response and septic shock [3].Susceptibility to gram-negative bacteria in human populations has been associated with allelic variation at TLR4 [4,5], with consequences for infectious, inflammatory and cardiovascular disease [6]. Yet the complexity of the innate i
%U http://www.biomedcentral.com/1471-2172/4/5