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 75708, USA.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.; Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA., Adduri S; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA., Ansari D; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.; Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA., John S; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.; Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA., Florence J; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA., Adejare O; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA., Singh G; Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA., Konduru N; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA., Jagannath C; Department of Pathology and Genomic Medicine, Center for Infectious Diseases and Translational Medicine, Houston Methodist Research Institute, Houston, TX, USA., Yi G; Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.; Center for Biomedical Research, The University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA.; Department of Medicine, The University of Texas at Tyler School of Medicine, Tyler, TX 75708, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Mar 07. Date of Electronic Publication: 2024 Mar 07.
DOI:	10.1101/2024.03.05.583545
Abstrakt:	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. Further, co-infections with HIV and Mtb have severe effects in the host, with people infected with HIV being fifteen to twenty-one times more likely to develop active TB. The use of an appropriate animal model for HIV/ Mtb co-infection that can recapitulate the diversity of the immune response in humans would be a useful tool for conducting basic and translational research in HIV/ Mtb infections. The present study was focused on developing a humanized mouse model for investigations on HIV- Mtb co-infection. Using NSG-SGM3 mice that can engraft human stem cells, our studies showed that they were able to engraft human CD34+ stem cells which then differentiate 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 the development of granulomatous lesions in the lungs, detected by CT scan and histopathology. Distinct metabolomic profiles were also observed in the tissues from different mouse groups after co-infections. Our results suggest that the humanized NSG-SGM3 mice are able to recapitulate the effects of HIV and Mtb infections and co-infection in the human host at pathological, immunological and metabolism levels, providing a dependable small animal model for studying HIV/ Mtb co-infection. Competing Interests: Competing interests All the authors declare no competing interests.
Databáze:	MEDLINE
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