Naturalizing mouse models for immunology

Graham, Andrea L.

doi:10.1038/s41590-020-00857-2

Cited by 72 publications

(73 citation statements)

References 83 publications

(134 reference statements)

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“…Recent paradigm-shifting work illustrated that lab mice are too far removed from natural environmental conditions to reliably mirror the physiology of free-living mammals like humans (212)(213)(214)(215). This circumstance distorts how the immune system of ultra-clean lab mice develops and functions, leading to false assumptions of how the human immune system works as reviewed elsewhere (216,217). To address these shortcomings several approaches have been suggested: Cohousing of lab mice with pet store mice (212), sequential infections of lab mice (213), rewilding of lab mice in semi-natural habitats (214), engraftment of wild mouse gut microbiota into lab mice (215) and the transfers of lab mouse embryos into wild mouse surrogate mothers, the so-called "wildling" model (218).…”

Section: Discussion and Outlookmentioning

confidence: 99%

The Mammalian Metaorganism: A Holistic View on How Microbes of All Kingdoms and Niches Shape Local and Systemic Immunity

Runge

Rosshart

2021

Front. Immunol.

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The field of microbiome research has developed rapidly over the past decades and has become a topic of major interest to basic, preclinical, and clinical research, the pharmaceutical industry as well as the general public. The microbiome is a complex and diverse ecosystem and defined as the collection of all host-associated microorganisms and their genes. It is acquired through vertical transmission and environmental exposure and includes microbes of all kingdoms: bacteria, archaea, prokaryotic and eukaryotic viruses, fungi, protozoa, and the meiofauna. These microorganisms co-evolved with their respective hosts over millions of years, thereby establishing a mutually beneficial, symbiotic relationship on all epithelial barriers. Thus, the microbiome plays a pivotal role in virtually every aspect of mammalian physiology, particularly in the development, homeostasis, and function of the immune system. Consequently, the combination of the host genome and the microbial genome, together referred to as the metagenome, largely drives the mammalian phenotype. So far, the majority of studies have unilaterally focused on the gastrointestinal bacterial microbiota. However, recent work illustrating the impact of viruses, fungi, and protozoa on host immunity urges us towards a holistic view of the mammalian microbiome and the appreciation for its non-bacterial kingdoms. In addition, the importance of microbiota on epithelial barriers other than the gut as well as their systemic effects via microbially-derived biologically active compounds is increasingly recognized. Here, we want to provide a brief but comprehensive overview of the most important findings and the current knowledge on how microbes of all kingdoms and microbial niches shape local and systemic immunity in health and disease.

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Section: Discussion and Outlookmentioning

confidence: 99%

The Mammalian Metaorganism: A Holistic View on How Microbes of All Kingdoms and Niches Shape Local and Systemic Immunity

Runge

Rosshart

2021

Front. Immunol.

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“…‘Germ free’ murine models are also potentially an attractive option for modeling UTI and the gut microbiota/UTI axis, allowing exclusive colonization of certain pathogens or purposefully introduced commensal species. For immunological purposes, naturalizing mouse models can also be used to help translate research to humans ( Graham, 2021 ). The immune profiles of laboratory mice are different from that of human as they have a low density of mature T cells ( Beura et al., 2016 ) and lower LPS sensitivity which could lead to differences in pathogenesis and treatment responses in humans ( Graham, 2021 ).…”

Section: Animal Models For Studying Utimentioning

confidence: 99%

“…For immunological purposes, naturalizing mouse models can also be used to help translate research to humans ( Graham, 2021 ). The immune profiles of laboratory mice are different from that of human as they have a low density of mature T cells ( Beura et al., 2016 ) and lower LPS sensitivity which could lead to differences in pathogenesis and treatment responses in humans ( Graham, 2021 ). However, germ-free mice are more expensive and need specialized equipment and training ( Kennedy et al., 2018 ).…”

Section: Animal Models For Studying Utimentioning

confidence: 99%

Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems

Murray

Flores

Williams

et al. 2021

Front. Cell. Infect. Microbiol.

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Urinary tract infections (UTIs) are among the most common infectious diseases worldwide but are significantly understudied. Uropathogenic E. coli (UPEC) accounts for a significant proportion of UTI, but a large number of other species can infect the urinary tract, each of which will have unique host-pathogen interactions with the bladder environment. Given the substantial economic burden of UTI and its increasing antibiotic resistance, there is an urgent need to better understand UTI pathophysiology – especially its tendency to relapse and recur. Most models developed to date use murine infection; few human-relevant models exist. Of these, the majority of in vitro UTI models have utilized cells in static culture, but UTI needs to be studied in the context of the unique aspects of the bladder’s biophysical environment (e.g., tissue architecture, urine, fluid flow, and stretch). In this review, we summarize the complexities of recurrent UTI, critically assess current infection models and discuss potential improvements. More advanced human cell-based in vitro models have the potential to enable a better understanding of the etiology of UTI disease and to provide a complementary platform alongside animals for drug screening and the search for better treatments.

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“…Therefore, the group showed that the microbiota of wild animals excellently phenocopied human immune responses and that the reproducibility of preclinical studies could be enhanced using a model composed of natural microbiota and certain pathogens [ 252 ]. An excellent review on the effect of “naturalizing mouse models”, which of course goes well beyond the microbiome as it includes biotic and abiotic factors, has recently been published by Graham [ 253 ].…”

Section: How To Ensure Validitymentioning

confidence: 99%

Health Monitoring of Laboratory Rodent Colonies—Talking about (R)evolution

Buchheister

Bleich

2021

Animals

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The health monitoring of laboratory rodents is essential for ensuring animal health and standardization in biomedical research. Progress in housing, gnotobiotic derivation, and hygienic monitoring programs led to enormous improvement of the microbiological quality of laboratory animals. While traditional health monitoring and pathogen detection methods still serve as powerful tools for the diagnostics of common animal diseases, molecular methods develop rapidly and not only improve test sensitivities but also allow high throughput analyses of various sample types. Concurrently, to the progress in pathogen detection and elimination, the research community becomes increasingly aware of the striking influence of microbiome compositions in laboratory animals, affecting disease phenotypes and the scientific value of research data. As repeated re-derivation cycles and strict barrier husbandry of laboratory rodents resulted in a limited diversity of the animals’ gut microbiome, future monitoring approaches will have to reform—aiming at enhancing the validity of animal experiments. This review will recapitulate common health monitoring concepts and, moreover, outline strategies and measures on coping with microbiome variation in order to increase reproducibility, replicability and generalizability.

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Naturalizing mouse models for immunology

Cited by 72 publications

References 83 publications

The Mammalian Metaorganism: A Holistic View on How Microbes of All Kingdoms and Niches Shape Local and Systemic Immunity

The Mammalian Metaorganism: A Holistic View on How Microbes of All Kingdoms and Niches Shape Local and Systemic Immunity

Recurrent Urinary Tract Infection: A Mystery in Search of Better Model Systems

Health Monitoring of Laboratory Rodent Colonies—Talking about (R)evolution

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