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Modeling Infectious Diseases in Mice with a “Humanized” Immune System

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  • Authors: Yan Li1,2, James P. Di Santo3,4
  • Editors: Pascale Cossart5, Craig R. Roy6, Philippe Sansonetti7
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Innate Immunity Unit, Immunology Department, Institut Pasteur, Paris, France; 2: Inserm U1223, Paris, France; 3: Innate Immunity Unit, Immunology Department, Institut Pasteur, Paris, France; 4: Inserm U1223, Paris, France; 5: Institut Pasteur, Paris, France; 6: Yale University School of Medicine, New Haven, Connecticut; 7: Institut Pasteur, Paris, France
  • Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0019-2019
  • Received 29 August 2018 Accepted 10 January 2019 Published 05 April 2019
  • James P. Di Santo, [email protected]
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  • Abstract:

    Human immune system (HIS) mice are created by transplanting human immune cells or their progenitor cells into highly immunodeficient recipient mouse hosts, thereby “humanizing” their immune systems. Over past decades, the field of HIS mice has evolved rapidly, as modifications of existing immunodeficient mouse strains have been developed, resulting in increasing levels of human tissue engraftment as humanization is optimized. Current HIS mouse models not only permit elevated levels of human cell engraftment but also demonstrate graft stability. As such, HIS mice are being extensively used to study the human innate and adaptive immune response against microbial infections . Compared to nonhumanized animal models, which are frequently infected with surrogate or adapted microbes, the HIS mouse models allow the analysis of interactions between human immune cells and pathogenic microbes, making them a more clinically relevant model. This article reviews the development of HIS mice and covers the different strategies used to humanize mice, as well as discussing the use of HIS mice for studying bacterial infections that cause human disease.

  • Citation: Li Y, Di Santo J. 2019. Modeling Infectious Diseases in Mice with a “Humanized” Immune System. Microbiol Spectrum 7(2):BAI-0019-2019. doi:10.1128/microbiolspec.BAI-0019-2019.

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/content/journal/microbiolspec/10.1128/microbiolspec.BAI-0019-2019
2019-04-05
2019-10-15

Abstract:

Human immune system (HIS) mice are created by transplanting human immune cells or their progenitor cells into highly immunodeficient recipient mouse hosts, thereby “humanizing” their immune systems. Over past decades, the field of HIS mice has evolved rapidly, as modifications of existing immunodeficient mouse strains have been developed, resulting in increasing levels of human tissue engraftment as humanization is optimized. Current HIS mouse models not only permit elevated levels of human cell engraftment but also demonstrate graft stability. As such, HIS mice are being extensively used to study the human innate and adaptive immune response against microbial infections . Compared to nonhumanized animal models, which are frequently infected with surrogate or adapted microbes, the HIS mouse models allow the analysis of interactions between human immune cells and pathogenic microbes, making them a more clinically relevant model. This article reviews the development of HIS mice and covers the different strategies used to humanize mice, as well as discussing the use of HIS mice for studying bacterial infections that cause human disease.

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Image of FIGURE 1
FIGURE 1

Timeline for development of immunodeficient mouse strains that form the basis for current HIS models. Indicated strains are described in the text.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0019-2019
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FIGURE 2

Boosting immune subsets in humanized mice. Cytokines and growth factor supplementation (left) in HIS mice can promote the expansion, differentiation, and function of selected hematopoietic lineages (right). TPO, thrombopoietin.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0019-2019
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FIGURE 3

Studying human pathogens in humanized mice. A variety of human pathogens, including viruses, bacteria, and parasites, have been analyzed in HIS mouse models. EBV, Epstein-Barr virus; CMV, cytomegalovirus; HTLV-1, human T cell leukemia virus type 1; KSHV, Kaposi’s sarcoma-associated herpesvirus.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0019-2019
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