The Trouble with "Clean" Mice: How Infection History Alters Host Immune Responses
Magdalena Chlebicz1, Tiffany A Reese1,2
11Department of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA;
Abstract:
Laboratory mice are widely used in biomedical research due to their low cost, genetic tractability, and ease of manipulation. To reduce experimental variability, they are typically housed under specific pathogen-free (SPF) conditions that limit microbial exposure. While this approach minimizes confounding infections, it also creates an immunological environment that differs markedly from that of humans, reducing the translational relevance of mouse immune studies. This limitation has driven the development of alternative models known as "dirty" or microbially experienced (ME) mice. Despite methodological differences, ME models demonstrate that lifelong microbial exposure profoundly shapes immune development. Although immune maturation in these mice is often attributed to microbiome changes, persistent exposure to endemic rodent viruses and other pathogens also may drive sustained immune activation. Here, we review the immune implications of the various ME models and highlight the critical role the virome plays in aligning mouse immune responses more closely with those of humans. Through harnessing microbial experience as a complementary tool to traditional SPF housing conditions and germ-free models, researchers can more faithfully model a mature, pathogen-shaped immune system.
Insights
Microbially experienced (ME) mice, exposed to pathogens, offer a more accurate model of the human immune system than standard specific pathogen-free (SPF) mice. The virome significantly influences immune development in these ME models.
Area of Science:
- Immunology
- Microbiology
- Animal Models
Background:
- Specific pathogen-free (SPF) mice are standard in research but have limited translational relevance due to their sterile environment.
- This sterile environment creates an immunological profile distinct from humans, impacting the validity of immune studies.
- Microbially experienced (ME) mice, exposed to a broader range of microbes, are being explored as alternatives.
Purpose of the Study:
- To review the immune implications of various microbially experienced (ME) mouse models.
- To highlight the role of the virome in shaping immune responses in ME mice.
- To assess the potential of ME models in better reflecting human immune system maturation.
Main Methods:
- Review of existing literature on ME mouse models and their immunological outcomes.
- Analysis of the impact of lifelong microbial exposure, including viral pathogens, on immune development.
- Comparison of immune profiles in SPF, ME, and germ-free mouse models.
Main Results:
- Lifelong microbial exposure in ME mice profoundly shapes immune development.
- Persistent exposure to endemic viruses and pathogens contributes to sustained immune activation in ME mice.
- The virome plays a critical role in aligning mouse immune responses with human responses.
Conclusions:
- ME mouse models offer a more faithful representation of a mature, pathogen-shaped immune system compared to SPF models.
- Harnessing microbial experience in mouse models can improve the translational relevance of immunological research.
- The virome is a key factor to consider when utilizing ME mice for studying human immunity.
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