Humanised Mouse Models: Recent Advances in Human Infectious Diseases

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (30 October 2023) | Viewed by 8958

Special Issue Editors


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Guest Editor
National Institute for Biological Standards and Control, Hertfordshire, UK
Interests: infectious diseases

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Co-Guest Editor
Taconic Biosciences GmbH, Leverkusen, Germany
Interests: infectious diseases

Special Issue Information

Dear Colleagues,

Since the generation of the first immunodeficient mice, humanised mouse models have considerably evolved and improved. Humanisation of immunodeficient mice can be achieved by engrafting different human cells, such as haematopoietic stem cells, PBMCs, erythrocytes, or hepatocytes. The use of these models enables in vivo investigations of human-restricted pathogens and human immune responses to these pathogens. Humanised mouse models have been developed for many infectious diseases such as malaria, COVID-19, tuberculosis, and schistosomiasis. While imperfect, these models can offer important insights into host–pathogen interactions, therapeutics, and vaccine efficacy. In this Special Issue, recent advances in our understanding of pathogens will be explored, along with the remaining challenges and opportunities in the field.

Dr. Adéla Nacer
Dr. Ivan E. Gladwyn-Ng
Guest Editors

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Keywords

  • humanised mice
  • infectious diseases
  • immunity
  • host–pathogen interactions
  • malaria
  • COVID-19
  • tuberculosis
  • schistosomiasis

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Published Papers (3 papers)

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Research

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19 pages, 4715 KiB  
Article
A Comparison of Lymphoid and Myeloid Cells Derived from Human Hematopoietic Stem Cells Xenografted into NOD-Derived Mouse Strains
by Hernando Gutierrez-Barbosa, Sandra Medina-Moreno, Federico Perdomo-Celis, Harry Davis, Carolina Coronel-Ruiz, Juan C. Zapata and Joel V. Chua
Microorganisms 2023, 11(6), 1548; https://doi.org/10.3390/microorganisms11061548 - 10 Jun 2023
Cited by 4 | Viewed by 3648
Abstract
Humanized mice are an invaluable tool for investigating human diseases such as cancer, infectious diseases, and graft-versus-host disease (GvHD). However, it is crucial to understand the strengths and limitations of humanized mice and select the most appropriate model. In this study, we describe [...] Read more.
Humanized mice are an invaluable tool for investigating human diseases such as cancer, infectious diseases, and graft-versus-host disease (GvHD). However, it is crucial to understand the strengths and limitations of humanized mice and select the most appropriate model. In this study, we describe the development of the human lymphoid and myeloid lineages using a flow cytometric analysis in four humanized mouse models derived from NOD mice xenotransplanted with CD34+ fetal cord blood from a single donor. Our results showed that all murine strains sustained human immune cells within a proinflammatory environment induced by GvHD. However, the Hu-SGM3 model consistently generated higher numbers of human T cells, monocytes, dendritic cells, mast cells, and megakaryocytes, and a low number of circulating platelets showing an activated profile when compared with the other murine strains. The hu-NOG-EXL model had a similar cell development profile but a higher number of circulating platelets with an inactivated state, and the hu-NSG and hu-NCG developed low frequencies of immune cells compared with the other models. Interestingly, only the hu-SGM3 and hu-EXL models developed mast cells. In conclusion, our findings highlight the importance of selecting the appropriate humanized mouse model for specific research questions, considering the strengths and limitations of each model and the immune cell populations of interest. Full article
(This article belongs to the Special Issue Humanised Mouse Models: Recent Advances in Human Infectious Diseases)
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Review

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16 pages, 901 KiB  
Review
Current Advances in Humanized Mouse Models for Studying NK Cells and HIV Infection
by Jocelyn T. Kim, Gabrielle Bresson-Tan and Jerome A. Zack
Microorganisms 2023, 11(8), 1984; https://doi.org/10.3390/microorganisms11081984 - 2 Aug 2023
Cited by 5 | Viewed by 2978
Abstract
Human immunodeficiency virus (HIV) has infected millions of people worldwide and continues to be a major global health problem. Scientists required a small animal model to study HIV pathogenesis and immune responses. To this end, humanized mice were created by transplanting human cells [...] Read more.
Human immunodeficiency virus (HIV) has infected millions of people worldwide and continues to be a major global health problem. Scientists required a small animal model to study HIV pathogenesis and immune responses. To this end, humanized mice were created by transplanting human cells and/or tissues into immunodeficient mice to reconstitute a human immune system. Thus, humanized mice have become a critical animal model for HIV researchers, but with some limitations. Current conventional humanized mice are prone to death by graft versus host disease induced by the mouse signal regulatory protein α and CD47 signaling pathway. In addition, commonly used humanized mice generate low levels of human cytokines required for robust myeloid and natural killer cell development and function. Here, we describe recent advances in humanization procedures and transgenic and knock-in immunodeficient mice to address these limitations. Full article
(This article belongs to the Special Issue Humanised Mouse Models: Recent Advances in Human Infectious Diseases)
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Other

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7 pages, 1107 KiB  
Brief Report
Using Cryopreserved Plasmodium falciparum Sporozoites in a Humanized Mouse Model to Study Early Malaria Infection Processes and Test Prophylactic Treatments
by María-Belén Jiménez-Díaz, Jörg J. Möhrle, Iñigo Angulo-Barturen and Claudia Demarta-Gatsi
Microorganisms 2023, 11(9), 2209; https://doi.org/10.3390/microorganisms11092209 - 31 Aug 2023
Cited by 2 | Viewed by 1660
Abstract
In addition to vector control, long-lasting insecticidal nets and case management, the prevention of infection through vaccination and/or chemoprevention are playing an increasing role in the drive to eradicate malaria. These preventative approaches represent opportunities for improvement: new drugs may be discovered that [...] Read more.
In addition to vector control, long-lasting insecticidal nets and case management, the prevention of infection through vaccination and/or chemoprevention are playing an increasing role in the drive to eradicate malaria. These preventative approaches represent opportunities for improvement: new drugs may be discovered that target the early infectious stages of the Plasmodium parasite in the liver (rather than the symptomatic, abundant blood stage), and new, exciting vaccination technologies have recently been validated (using mRNA or novel adjuvants). Exploiting these possibilities requires the availability of humanized mouse models that support P. falciparum infection yet avoid the hazardous use of infectious mosquitoes. Here, we show that commercially available P. falciparum sporozoites and FRG mice carrying human hepatocytes and red blood cells faithfully recapitulate the early human malaria disease process, presenting an opportunity to use this model for the evaluation of prophylactic treatments with a novel mode of action. Full article
(This article belongs to the Special Issue Humanised Mouse Models: Recent Advances in Human Infectious Diseases)
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