Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination
ABSTRACTSpecific 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 a...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2024-02-01
|
| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00654-23 |
| _version_ | 1797292557511688192 |
|---|---|
| author | Autumn E. Sanders Henriette Arnesen Frances K. Shepherd Dira S. Putri Jessica K. Fiege Mark J. Pierson Shanley N. Roach Harald Carlsen David Masopust Preben Boysen Ryan A. Langlois |
| author_facet | Autumn E. Sanders Henriette Arnesen Frances K. Shepherd Dira S. Putri Jessica K. Fiege Mark J. Pierson Shanley N. Roach Harald Carlsen David Masopust Preben Boysen Ryan A. Langlois |
| author_sort | Autumn E. Sanders |
| collection | DOAJ |
| description | ABSTRACTSpecific 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.IMPORTANCEAnimal 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. |
| first_indexed | 2024-03-07T19:58:10Z |
| format | Article |
| id | doaj.art-87adcac41ea74783bc1ecd64e40dff96 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-03-07T19:58:10Z |
| publishDate | 2024-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-87adcac41ea74783bc1ecd64e40dff962024-02-28T14:07:38ZengAmerican Society for MicrobiologymSphere2379-50422024-02-019210.1128/msphere.00654-23Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccinationAutumn E. Sanders0Henriette Arnesen1Frances K. Shepherd2Dira S. Putri3Jessica K. Fiege4Mark J. Pierson5Shanley N. Roach6Harald Carlsen7David Masopust8Preben Boysen9Ryan A. Langlois10Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USAFaculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, NorwayDepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USADepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USADepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USACenter for Immunology, University of Minnesota, Minneapolis, Minnesota, USADepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USAFaculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, NorwayDepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USAFaculty of Veterinary Medicine, Norwegian University of Life Sciences, Ås, NorwayDepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USAABSTRACTSpecific 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.IMPORTANCEAnimal 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.https://journals.asm.org/doi/10.1128/msphere.00654-23mouse modelsvaccinesnatural mouse virusespreclinical models |
| spellingShingle | Autumn E. Sanders Henriette Arnesen Frances K. Shepherd Dira S. Putri Jessica K. Fiege Mark J. Pierson Shanley N. Roach Harald Carlsen David Masopust Preben Boysen Ryan A. Langlois Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination mSphere mouse models vaccines natural mouse viruses preclinical models |
| title | Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination |
| title_full | Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination |
| title_fullStr | Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination |
| title_full_unstemmed | Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination |
| title_short | Comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination |
| title_sort | comparison of mouse models of microbial experience reveals differences in microbial diversity and response to vaccination |
| topic | mouse models vaccines natural mouse viruses preclinical models |
| url | https://journals.asm.org/doi/10.1128/msphere.00654-23 |
| work_keys_str_mv | AT autumnesanders comparisonofmousemodelsofmicrobialexperiencerevealsdifferencesinmicrobialdiversityandresponsetovaccination AT henriettearnesen comparisonofmousemodelsofmicrobialexperiencerevealsdifferencesinmicrobialdiversityandresponsetovaccination AT franceskshepherd comparisonofmousemodelsofmicrobialexperiencerevealsdifferencesinmicrobialdiversityandresponsetovaccination AT dirasputri comparisonofmousemodelsofmicrobialexperiencerevealsdifferencesinmicrobialdiversityandresponsetovaccination AT jessicakfiege comparisonofmousemodelsofmicrobialexperiencerevealsdifferencesinmicrobialdiversityandresponsetovaccination AT markjpierson comparisonofmousemodelsofmicrobialexperiencerevealsdifferencesinmicrobialdiversityandresponsetovaccination AT shanleynroach comparisonofmousemodelsofmicrobialexperiencerevealsdifferencesinmicrobialdiversityandresponsetovaccination AT haraldcarlsen comparisonofmousemodelsofmicrobialexperiencerevealsdifferencesinmicrobialdiversityandresponsetovaccination AT davidmasopust comparisonofmousemodelsofmicrobialexperiencerevealsdifferencesinmicrobialdiversityandresponsetovaccination AT prebenboysen comparisonofmousemodelsofmicrobialexperiencerevealsdifferencesinmicrobialdiversityandresponsetovaccination AT ryanalanglois comparisonofmousemodelsofmicrobialexperiencerevealsdifferencesinmicrobialdiversityandresponsetovaccination |