Conservation and divergence in Toll-like receptor 4-regulated gene expression in primary human versus mouse macrophages

摘要

Mice are widely used as experimental models for human immunology, but these species are distant relatives. Moreover, as rapidly evolving pathogens exert intense pressure on the immune system to coevolve, substantial differences between these species' immune systems are likely. To help address these differences, we compared regulated gene expression in human and mouse immune cells in response to the archetypal inflammatory stimulus lipopoly-saccharide (LPS). We identified marked divergence in gene regulation between species (http://www.macgate.qfab.org/ index.htm), and found that dynamically regulated genes are exquisitely sensitive to evolutionary changes. Our study maps the strengths and weaknesses of the mouse model and identifies human-specific responses as therapeutic targets for infectious and inflammatory diseases.