Of Mice, Dirty Mice, and Men: Using Mice To Understand Human Immunology

Masopust, David; Sivula, Christine P.; Jameson, Stephen C.

doi:10.4049/jimmunol.1700453

Cited by 203 publications

(174 citation statements)

References 51 publications

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“…While model organisms are an irreplaceable tool in our understanding of the requirements for immunity, we must turn to the human model to fully understand the human system. The differing environs between humans and experimental mice, who are frequently housed in the absence of specific pathogens, are likely at least partially responsible for the functional distinctions between innate immune cell subsets between the species . There is also notable divergent evolution with a number of important of functional orthologues being represented by distinct gene families in humans and mice, such as Ly49 in mice and KIR in humans .…”

Section: Introductionmentioning

confidence: 99%

Emerging insights into human health and NK cell biology from the study of NK cell deficiencies

Mace

Orange

2018

Immunological Reviews

129

105

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Human NK cells are innate immune effectors that play a critical roles in the control of viral infection and malignancy. The importance of their homeostasis and function can be demonstrated by the study of patients with primary immunodeficiencies (PID), which are part of the family of diseases known as inborn defects of immunity. While NK cells are affected in many PIDs in ways that may contribute to a patient’s clinical phenotype, a small number of PIDs have an NK cell abnormality as their major immunological defect. These PIDs can be collectively referred to as NK cell deficiency disorders (NKD), and include effects upon NK cell numbers, subsets and/or functions. The clinical impact of NKD can be severe including fatal viral infection, with particular susceptibility to herpesviral infections, such as cytomegalovirus, varicella zoster virus and Epstein-Barr virus. While NKD is rare, studies of these diseases are important for defining specific requirements for human NK cell development and homeostasis. New themes in NK cell biology are emerging through the study of both known and novel NKD, particularly those affecting cell cycle and DNA damage repair, as well as broader PIDs having substantive impact upon NK cells. In addition, the discovery of NKD that affect other innate lymphoid cell (ILC) subsets opens new doors for better understanding the relationship between conventional NK cells and other ILC subsets. Here we describe the biology underlying human NKD, particularly in the context of new insights into innate immune cell function, including a discussion of recently described NKD with accompanying effects on ILC subsets. Given the impact of these disorders upon human immunity with a common focus upon NK cells, the unifying message of a critical role for NK cells in human host defense singularly emerges.

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Section: Introductionmentioning

confidence: 99%

Emerging insights into human health and NK cell biology from the study of NK cell deficiencies

Mace

Orange

2018

Immunological Reviews

129

105

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“…Collect and appropriately document and store specimens needed for assays described in point 3, and as applicable, fecal, or other relevant samples to facilitate assessment of any association of the gut microbiota with differential responses. 181,182 In their natural environment mice, like humans, are exposed to microbes, including pathogens, and thus should be regarded as metaorganisms, with their own specific microbiota (including bacteria, fungi, and viruses). 195 or questions.…”

Section: Validated Methods For De-risking the Npct (See Alsomentioning

confidence: 99%

Improving natural product research translation: From source to clinical trial

et al. 2019

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While great interest in health effects of natural product (NP) including dietary supplements and foods persists, promising preclinical NP research is not consistently translating into actionable clinical trial (CT) outcomes. Generally considered the gold standard for assessing safety and efficacy, CTs, especially phase III CTs, are costly and require rigorous planning to optimize the value of the information obtained. More effective bridging from NP research to CT was the goal of a Septe mber, 2018 trans disci plina ry workshop. Participants emphasized that replicability and likelihood of successful translation depend on rigor in experimental design, interpretation, and reporting across the continuum of NP research. Discussions spanned good practices for NP characterization and quality control; use and interpretation of models (computational through in vivo) with strong clinical predictive validity; controls for experimental artefacts, especially for in vitro interrogation of bioactivity and mechanisms of action; rigorous assessment and interpretation of prior research; transparency in all reporting; and prioritization of research questions. Natural product clinical trials prioritized based on rigorous, convergent supporting data and current public health needs are most likely to be informative and ultimately affect public health. Thoughtful, coordinated implementation of these practices should enhance the knowledge gained from future NP research. K E Y W O R D S clinical predictive validity, dietary supplements, model systems, rigor and replicability, value of information | 43 SORKIN et al.still provide invaluable guidance, the results of such trials are often met with concerns that different design choiceswhether of product, dose, timing, participant eligibility criteria, outcomes, etc.-might have yielded a substantially different result. Each interventional trial represents a substantial investment, with well-powered Phase III CTs typically consuming more than $10 million and many person-years. 9,10 Additionally, as time and funds are limited, and participant pools may also be constrained, a decision to invest in a CT often precludes pursuing other research questions, 11 which may provide more useful public health-relevant knowledge than an RCT with an insufficient evidence base.

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“…The dominance of the mouse as a model system is driven by several factors, including their relatively low cost, ease of housing, and their rapid reproduction times and large litter sizes. 23 Importantly, the availability of inbred mouse strains, in which every mouse in the strain is essentially genetically identical, as well as genetically modified mice lacking specific host genes, 24,25 has allowed the scientific research community to study how specific host genes affect the response to pathogen challenge while also promoting understanding of the host immune system and its role in protecting from pathogen challenge or mediating vaccine-induced immunity. 26 Mouse models do have limitations, including physiologic differences that limit how well mice reproduce key aspects of hostepathogen interactions, such as efficient influenza virus transmission.…”

Section: Introductionmentioning

confidence: 99%

Mouse Models as Resources for Studying Infectious Diseases

Sarkar

Heise

2019

Clinical Therapeutics

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Mouse models are important tools both for studying the pathogenesis of infectious diseases and for the preclinical evaluation of vaccines and therapies against a wide variety of human pathogens. The use of genetically defined inbred mouse strains, humanized mice, and gene knockout mice has allowed the research community to explore how pathogens cause disease, define the role of specific host genes in either controlling or promoting disease, and identify potential targets for the prevention or treatment of a wide range of infectious agents. This review discusses several of the most commonly used mouse model systems, as well as new resources such as the Collaborative Cross as models for studying infectious diseases. (Clin Ther. 2019;41:1912e1922)

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Of Mice, Dirty Mice, and Men: Using Mice To Understand Human Immunology

Cited by 203 publications

References 51 publications

Emerging insights into human health and NK cell biology from the study of NK cell deficiencies

Emerging insights into human health and NK cell biology from the study of NK cell deficiencies

Improving natural product research translation: From source to clinical trial

Mouse Models as Resources for Studying Infectious Diseases

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