Humanized Mouse Model Mimicking Pathology of Human Tuberculosis for in vivo Evaluation of Drug Regimens
| Autor: | Martin Gengenbacher, Tatsiana Skrahina, Laura Lozza, Stefanie Kuhlmann, Frida Arrey, Pedro Moura-Alves, Geraldine Nouailles, Delia Löwe, Peggy Kaiser, Alena Skrahina, Gopinath Krishnamoorthy, Jeroen Maertzdorf, Stefan H. E. Kaufmann |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine lcsh:Immunologic diseases. Allergy Pathology medicine.medical_specialty Tuberculosis Moxifloxacin Immunology Antitubercular Agents antibiotics lung Mycobacterium tuberculosis humanized mouse models Mice 03 medical and health sciences 0302 clinical medicine Immune system In vivo medicine Animals Humans Immunology and Allergy granuloma Tuberculosis Pulmonary human immune system mice Original Research biology business.industry Hematopoietic Stem Cell Transplantation medicine.disease biology.organism_classification Chemotherapy regimen infection 3. Good health Mice Inbred C57BL Disease Models Animal 030104 developmental biology Drug development Granuloma Humanized mouse pathology Drug Therapy Combination Female business lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in immunology Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology |
| Popis: | Human immune system mice are highly valuable for in vivo dissection of human immune responses. Although they were employed for analyzing tuberculosis (TB) disease, there is little data on the spatial organization and cellular composition of human immune cells in TB granuloma pathology in this model. We demonstrate that human immune system mice, generated by transplanted human fetal liver derived hematopoietic stem cells develop a continuum of pulmonary lesions upon Mycobacterium tuberculosis aerosol infection. In particular, caseous necrotic granulomas, which contribute to prolonged TB treatment time, developed, and had cellular phenotypic spatial-organization similar to TB patients. By comparing two recommended drug regimens, we confirmed observations made in clinical settings: Adding Moxifloxacin to a classical chemotherapy regimen had no beneficial effects on bacterial eradication. We consider this model instrumental for deeper understanding of human specific features of TB pathogenesis and of particular value for the pre-clinical drug development pipeline. |
| Databáze: | OpenAIRE |
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