Ilya Metchnikoff's use of starfish larvae to discover phagocytosis, and Bruno Lemaitre's and Jules Hoffmann's identification of host defence functions for Drosophila Toll provide compelling examples of the utility of model organisms for discovery of human innate immune pathways. Bruce Beutler's mapping of lipopolysaccharide non-responsiveness in C3H/HeJ mice to the Toll-like Receptor 4 gene similarly highlights the power of the mouse as a model. Models have limitations however, and characterising the functional relevance of human innate immune responses not conserved in the mouse presents both a challenge and an opportunity. Here we review differences between human and mouse Toll-like Receptors and inflammasome-forming Nod-like Receptors in repertoire, regulation and function, highlighting the significance of these differences for human innate immunity.

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