A novel humanized mouse model for HIV and tuberculosis co-infection studies.

Autor:	Bohórquez JA; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX, United States., Adduri S; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, United States., Ansari D; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX, United States., John S; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX, United States., Florence J; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, United States., Adejare O; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, United States., Singh G; Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX, United States., Konduru NV; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, United States., Jagannath C; Department of Pathology and Genomic Medicine, Center for Infectious Diseases and Translational Medicine, Houston Methodist Research Institute, Houston, TX, United States., Yi G; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX, United States.; Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 May 10; Vol. 15, pp. 1395018. Date of Electronic Publication: 2024 May 10 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1395018
Abstrakt:	Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis ( Mtb ), continues to be a major public health problem worldwide. The human immunodeficiency virus (HIV) is another equally important life-threatening pathogen. HIV infection decreases CD4+ T cell levels markedly increasing Mtb co-infections. An appropriate animal model for HIV/ Mtb co-infection that can recapitulate the diversity of the immune response in humans during co-infection would facilitate basic and translational research in HIV/ Mtb infections. Herein, we describe a novel humanized mouse model. Methods: The irradiated NSG-SGM3 mice were transplanted with human CD34+ hematopoietic stem cells, and the humanization was monitored by staining various immune cell markers for flow cytometry. They were challenged with HIV and/or Mtb , and the CD4+ T cell depletion and HIV viral load were monitored over time. Before necropsy, the live mice were subjected to pulmonary function test and CT scan, and after sacrifice, the lung and spleen homogenates were used to determine Mtb load (CFU) and cytokine/chemokine levels by multiplex assay, and lung sections were analyzed for histopathology. The mouse sera were subjected to metabolomics analysis. Results: Our humanized NSG-SGM3 mice were able to engraft human CD34+ stem cells, which then differentiated into a full-lineage of human immune cell subsets. After co-infection with HIV and Mtb , these mice showed decrease in CD4+ T cell counts overtime and elevated HIV load in the sera, similar to the infection pattern of humans. Additionally, Mtb caused infections in both lungs and spleen, and induced granulomatous lesions in the lungs. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. Conclusion: The humanized NSG-SGM3 mice are able to recapitulate the pathogenic effects of HIV and Mtb infections and co-infection at the pathological, immunological and metabolism levels and are therefore a reproducible small animal model for studying HIV/ Mtb co-infection. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Bohórquez, Adduri, Ansari, John, Florence, Adejare, Singh, Konduru, Jagannath and Yi.)
Databáze:	MEDLINE
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