ArticleProceedings of the National Academy of Sciences of the United States of America2013
CD4+ cell-dependent granuloma formation in humanized mice infected with mycobacteria.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
- Trial
- Applications of humanized mice inMolecular medicine reports · 2026Review
- Infection dose shapes granuloma phenotypes in a humanized mouse model of tuberculosis.Research square · 2026Article
- Testing the capacity of humanized immune system mice to induce a protective antibody response against the Lyme disease pathogen.Microbiology spectrum · 2026Article
- T Cell Responses during Human Immunodeficiency Virus/Vaccines · 2024Review
- Article
- Humanized Mouse Models of Bacterial Infections.Antibiotics (Basel, Switzerland) · 2024Review
- Antigen identification strategies and preclinical evaluation models for advancing tuberculosis vaccine development.NPJ vaccines · 2024Review
- Development of animal models for emerging infectious diseases by breaking the barrier of species susceptibility to human pathogens.Emerging microbes & infections · 2023Article
- Intranasal multivalent adenoviral-vectored vaccine protects against replicating and dormant M.tb in conventional and humanized mice.NPJ vaccines · 2023Article
- Comparing Current and Next-Generation Humanized Mouse Models for Advancing HIV and HIV/Viruses · 2022Article
- Advancing our understanding of HIV co-infections and neurological disease using the humanized mouse.Retrovirology · 2021Review
- Lung Injury on Antiretroviral Therapy in Adults With Human Immunodeficiency Virus/Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- Advances in Humanized Mouse Models to Improve Understanding of HIV-1 Pathogenesis and Immune Responses.Frontiers in immunology · 2020Review
- Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis.BioMed research international · 2020Review
- Humanized mouse models reveal an immunologic classification of idiopathic CD4 lymphocytopenia subtypes.JCI insight · 2019Article
- Immunology ofMicrobiology spectrum · 2019Review
- Modeling Infectious Diseases in Mice with a "Humanized" Immune System.Microbiology spectrum · 2019Review
- Humanized Mouse Model Mimicking Pathology of Human Tuberculosis forFrontiers in immunology · 2019Article
- Animal models of tuberculosis: Lesson learnt.The Indian journal of medical research · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have used humanized mice, in which human immune cells differentiate de novo from transplanted cord blood progenitor cells, to study the human immune responses to infection with Mycobacterium bovis bacillus Calmette-Guérin and Mycobacterium tuberculosis. Granulomas with a core containing giant cells, human CD68(+) macrophages, and high bacilli numbers surrounded by a layer of CD3(+) T cells and a fibrotic response encapsulating the lesions were observed in livers and lungs from bacillus Calmette-Guérin-infected humanized mice but not in nonhumanized infected controls. Paradoxically, humanized mice contained higher mycobacterial numbers in organs than nonhumanized controls. The enhancement of bacterial load was mediated by human CD4(+) cells and associated to an increased expression of Programmed Death-1 protein and CD57 on T cells, molecules associated with inhibition and senescence. The lesions from mice depleted of CD4(+) cells were scarcer, minimal, and irregular compared with those from mice depleted of CD8(+) cells or nondepleted controls. Granulomas of bacillus Calmette-Guérin-infected humanized mice administered with a TNF-neutralizing TNF receptor fusion molecule preserved their structure, but contained higher levels of intracellular bacilli. Extended necrosis was observed in granulomas from M. tuberculosis- but not bacillus Calmette-Guérin-infected humanized mice. Our data indicate that humanized mice can be used as a model to study the formation and maintenance of human granuloma in tuberculosis and other infectious or noninfectious diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.