last updated April 2013
Of mice and men
A study of human and mouse immune responses shows surprisingly different reactions to the same microbial stimulus
Studies of human immune responses frequently use the mouse as a model. However, immune systems must evolve quickly to keep pace with rapidly evolving pathogens, and the mouse therefore has some limitations as a model for human immunity. A study led by Kate Schroder and Katharine Irvine at the University of Queensland, Australia and Martin Taylor at the European Bioinformatics Institute in Cambridge, UK compared human and mouse responses to the same microbial stimulus. They found that 24% of the genes switched on or off in response to this challenge differed between the species.1
Schroder’s team challenged cultures of human and mouse immune cells with an immunostimulatory cell wall component from Salmonella. They monitored which genes were turned on and off, to what degree, and for how long. Each species responded with an arsenal of unique defenses, consistent with the strong evolutionary pressure pathogens exert on their hosts.
The researchers also studied the evolutionary forces that shaped divergence. They investigated how gene regulation evolves by comparing gene-control switches called promoters between mice and humans. Paradoxically, promoter sequences of differently regulated genes changed very little over evolutionary time. These promoters were complex, integrating many inputs, suggesting they can produce a wide variety of responses to environmental or evolutionary pressures, without themselves changing.