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 bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities.
The group caught mice in barns or purchased them at pet stores and carefully compared their immune system to that of humans. The free-living, or dirty, mice better mirrored immune cell types and tissue distribution found in adult humans. In contrast, the immune system in lab mice which are sheltered from natural microbial exposure were more strongly matched with newborn humans.
Lab mice lacked 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.
When genetically homogenous lab mice were co-housed with dirty mice this restored more normal microbial experience and allowed the immune system of the lab mice to adapt and better recapitulate the adult human immune system. Memory T cells 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.
"This model could provide an important addition to basic research into immunology and the many biological processes and diseases that are impacted by inflammation," said co-senior author. "Utilizing this model to test vaccinations and therapeutics for cancer or transplantation may better predict how these will perform in humans."
The use of standard lab mice has led to numerous breakthroughs in biomedical research, including studies that led to recent advances in cancer immunotherapy. However, this study shows the immune system in lab mice may not be fully normalized without a more complete microbial exposure.
Hence these so-called dirty mice offer a substantial advance over current models, providing increased translational potential for human disease and better therapeutic models without sacrificing established and powerful research tools.The results were published in the journal Nature.
Researchers show 'dirty mice' could clean up immune system research
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