Cohousing with Dirty Mice Increases the Frequency of Memory T Cells and Has Variable Effects on Intracellular Bacterial Infection

Labuda, Jasmine C.; Fong, K.; McSorley, Stephen J.

doi:10.4049/immunohorizons.2100069

Cited by 10 publications

(6 citation statements)

References 34 publications

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“…Despite the lower number of microbes compared to both types of cohousing, feralized mice do experience an alteration in basal immune activation resulting in significant phenotypes (e.g., protection against colorectal cancer) ( 18 ). These data are consistent with a recent study which observed an impact of cohousing with both pet store and wild mice on the immune systems of SPF mice but was weaker with wild animals which may have fewer microbes ( 11 ).…”

Section: Discussionsupporting

confidence: 93%

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Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination

Sanders,

Arnesen,

Shepherd

et al. 2024

mSphere

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Specific pathogen-free (SPF) laboratory mice dominate preclinical studies for immunology and vaccinology. Unfortunately, SPF mice often fail to accurately model human responses to vaccination and other immunological perturbations. Several groups have taken different approaches to introduce additional microbial experience to SPF mice to better model human immune experience. How these different models compare is unknown. Here, we directly compare three models: housing SPF mice in a microbe-rich barn-like environment (feralizing), adding wild-caught mice to the barn-like environment (fer-cohoused), or cohousing SPF mice with pet store mice in a barrier facility (pet-cohoused); the two latter representing different murine sources of microbial transmission. Pet-cohousing mice resulted in the greatest microbial exposure. Feralizing alone did not result in the transmission of any pathogens tested, while fer-cohousing resulted in the transmission of several picornaviruses. Murine astrovirus 2, the most common pathogen from pet store mice, was absent from the other two model systems. Previously, we had shown that pet-cohousing reduced the antibody response to vaccination compared with SPF mice. This was not recapitulated in either the feralized or fer-cohoused mice. These data indicate that not all dirty mouse models are equivalent in either microbial experience or immune responses to vaccination. These disparities suggest that more cross model comparisons are needed but also represent opportunities to uncover microbe combination-specific phenotypes and develop more refined experimental models. Given the breadth of microbes encountered by humans across the globe, multiple model systems may be needed to accurately recapitulate heterogenous human immune responses. IMPORTANCE Animal models are an essential tool for evaluating clinical interventions. Unfortunately, they can often fail to accurately predict outcomes when translated into humans. This failure is due in part to a lack of natural infections experienced by most laboratory animals. To improve the mouse model, we and others have exposed laboratory mice to microbes they would experience in the wild. Although these models have been growing in popularity, these different models have not been specifically compared. Here, we directly compare how three different models of microbial experience impact the immune response to influenza vaccination. We find that these models are not the same and that the degree of microbial exposure affects the magnitude of the response to vaccination. These results provide an opportunity for the field to continue comparing and contrasting these systems to determine which models best recapitulate different aspects of the human condition.

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Section: Discussionsupporting

confidence: 93%

“…The cohousing model is expanding in popularity ( 9 , 11 , 12 ). Differences in microbial experiences across these models offer an opportunity to evaluate the impact of heterogenous infections on the immune response.…”

Section: Discussionmentioning

confidence: 99%

Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination

Sanders,

Arnesen,

Shepherd

et al. 2024

mSphere

View full text Add to dashboard Cite

show abstract

“…To examine the long-term impact of early microbial exposure on immune susceptibility, we modified the pet-shop mouse model ( 26 – 28 ) to provide microbial exposure beginning in early gestation ( Fig. 1 A ).…”

Section: Resultsmentioning

confidence: 99%

Early microbial exposure shapes adult immunity by altering CD8+ T cell development

Tabilas

Daly

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Microbial exposure during development can elicit long-lasting effects on the health of an individual. However, how microbial exposure in early life leads to permanent changes in the immune system is unknown. Here, we show that the microbial environment alters the set point for immune susceptibility by altering the developmental architecture of the CD8+ T cell compartment. In particular, early microbial exposure results in the preferential expansion of highly responsive fetal-derived CD8+ T cells that persist into adulthood and provide the host with enhanced immune protection against intracellular pathogens. Interestingly, microbial education of fetal-derived CD8+ T cells occurs during thymic development rather than in the periphery and involves the acquisition of a more effector-like epigenetic program. Collectively, our results provide a conceptual framework for understanding how microbial colonization in early life leads to lifelong changes in the immune system.

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“…These data contribute an aging perspective to the literature comparing the immune response of “clean,” SPF-maintained laboratory mice and “dirty” mice, generated by a variety of methods, including sequential infection, cohousing with pet store or wild mice, or transfer of microbiota from wild mice ( 14–17 , 20–24 , 47 ). The published literature on immunity in dirty mice has shown variable results, with some studies showing enhanced immunity ( 17 , 47 , 48 ) and others showing depressed immunity ( 15 , 49 ) or no effect ( 48 ). Variations in these results likely reflect differences in the manner of inducing antigenic experience, the pathogen used to assess immunity, the type of immune responses analyzed, and the time points and/or age at which the assessments were undertaken.…”

Section: Discussionmentioning

confidence: 99%

Sequential Early-Life Infections Alter Peripheral Blood Transcriptomics in Aging Female Mice but Not the Response to De Novo Infection with Influenza Virus or M. tuberculosis

et al. 2023

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To determine the impact of accumulating Ag exposure on immunity in the aging mouse, and to develop a model more relevant to humans who are exposed to multiple pathogens during life, we sequentially infected young female mice with four distinct pathogens at 8-wk intervals: murine γ-herpesvirus 68, Sendai virus, murine CMV, and Heligmosomoides polygyrus. Mock-infected mice received PBS. After aging the sequentially infected and mock-infected mice to 18–25 mo under specific pathogen-free conditions, we analyzed multiple immune parameters. We assessed transcriptional activity in peripheral blood, T cell phenotype, the diversity of influenza epitopes recognized by CD8 T cells, and the response of the animals to infection with influenza virus and Mycobacterium tuberculosis. Our data show enhanced transcriptional activation in sequentially infected aged mice, with changes in some CD8 T cell subsets. However, there was no measurable difference in the response of mock-infected and sequentially infected aged mice to de novo infection with either influenza virus or M. tuberculosis at 18–21 mo. Unexpectedly, a single experiment in which 25-mo-old female mice were challenged with influenza virus revealed a significantly higher survival rate for sequentially infected (80%) versus mock-infected (20%) mice. These data suggest that although exposure to a variety of pathogen challenges in the mouse model does not overtly impact cellular markers of immunity in aged female mice following de novo respiratory infection, subtle changes may emerge in other compartments or with increasing age.

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Cohousing with Dirty Mice Increases the Frequency of Memory T Cells and Has Variable Effects on Intracellular Bacterial Infection

Cited by 10 publications

References 34 publications

Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination

Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination

Early microbial exposure shapes adult immunity by altering CD8+ T cell development

Sequential Early-Life Infections Alter Peripheral Blood Transcriptomics in Aging Female Mice but Not the Response to De Novo Infection with Influenza Virus or M. tuberculosis

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