Here's a link to the article (behind a paywall) mentioned above:For Immediate Release: Wednesday, April 20, 2016
“Dirty Mouse” May Model Human Immune System More Accurately,
NIH-Funded Study Suggests
Medical interventions that work well when tested in mouse models can fail when they advance to safety and efficacy testing in humans. One reason for this, scientists propose, may be the differences between immune system development in laboratory mice and humans. Laboratory mice are raised in pathogen-free environments lacking microbial diversity that may contribute to these differences, concludes a new study funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health. A scientific team led by David Masopust of the University of Minnesota found that co-housing laboratory mice with mice from pet stores can produce “dirty mouse” models that may better reflect the immune systems of adult human beings.
The research team first explored immunological differences between laboratory mice and humans by analyzing cervical tissue specimens from adults of each species. The researchers found that laboratory mice had fewer, less diverse and less widely distributed memory T cells, a type of immune cell, compared with humans. The immune systems of laboratory mice more closely resembled those of human infants, particularly with regard to the number and tissue distribution of memory T cells.
Next the researchers performed a similar analysis on tissues from laboratory mice and from mice found in barn or pet store environments. The non-laboratory mice had immune systems more like those of adult humans, suggesting the variation in microbial environment—and not the species difference—could account for the different immune system makeups.
The researchers then explored if the immune systems of laboratory mice with little exposure to environmental microbes could change when exposed to a different environment. They co-housed laboratory mice with healthy mice raised in a pet store. After eight weeks, analysis of the laboratory mice revealed patterns of T cells and other immune system components that more closely matched the pet store mice as well as adult humans. These findings suggest that “dirty mice” may model the human immune system more closely than typical laboratory mice and could be studied to learn more about the role of environment and genetics in the development of the human immune system.
D Masopust et al. Normalizing the Environment Recapitulates Adult Human Immune Traits in Laboratory Mice. Nature DOI: 10.1038/nature17655 (2016).
http://www.nature.com/nature/journal/va ... 17655.html
Normalizing the environment recapitulates adult human immune traits in laboratory mice
Nature (2016) doi:10.1038/nature17655
Received 21 January 2016 Accepted 11 March 2016 Published online 20 April 2016
Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside1, 2, 3, 4, 5, 6, 7, 8. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice—like newborn, but not adult, humans—lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.