A Humanized Mouse Model of Tuberculosis

Veronica E. Calderon, Gustavo Valbuena, Yenny Goez, Barbara M. Judy, Matthew Huante, Putri Sutjita, R. Katie Johnston, D. Mark Estes, Robert L. Hunter, Jeffrey K. Actor, Jeffrey D. Cirillo, Janice Endsley

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Mycobacterium tuberculosis (M.tb) is the second leading infectious cause of death worldwide and the primary cause of death in people living with HIV/AIDS. There are several excellent animal models employed to study tuberculosis (TB), but many have limitations for reproducing human pathology and none are amenable to the direct study of HIV/M.tb co-infection. The humanized mouse has been increasingly employed to explore HIV infection and other pathogens where animal models are limiting. Our goal was to develop a small animal model of M.tb infection using the bone marrow, liver, thymus (BLT) humanized mouse. NOD-SCID/γc null mice were engrafted with human fetal liver and thymus tissue, and supplemented with CD34+ fetal liver cells. Excellent reconstitution, as measured by expression of the human CD45 pan leukocyte marker by peripheral blood populations, was observed at 12 weeks after engraftment. Human T cells (CD3, CD4, CD8), as well as natural killer cells and monocyte/macrophages were all observed within the human leukocyte (CD45+) population. Importantly, human T cells were functionally competent as determined by proliferative capacity and effector molecule (e.g. IFN-γ, granulysin, perforin) expression in response to positive stimuli. Animals infected intranasally with M.tb had progressive bacterial infection in the lung and dissemination to spleen and liver from 2-8 weeks post infection. Sites of infection in the lung were characterized by the formation of organized granulomatous lesions, caseous necrosis, bronchial obstruction, and crystallization of cholesterol deposits. Human T cells were distributed throughout the lung, liver, and spleen at sites of inflammation and bacterial growth and were organized to the periphery of granulomas. These preliminary results demonstrate the potential to use the humanized mouse as a model of experimental TB.

Original languageEnglish (US)
Article numbere63331
JournalPLoS One
Volume8
Issue number5
DOIs
StatePublished - May 17 2013

Fingerprint

tuberculosis
Liver
Tuberculosis
animal models
T-cells
Animals
Mycobacterium tuberculosis
Thymus
liver
Animal Models
T-lymphocytes
lungs
mice
T-Lymphocytes
Lung
Thymus Gland
Perforin
Cause of Death
leukocytes
spleen

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Calderon, V. E., Valbuena, G., Goez, Y., Judy, B. M., Huante, M., Sutjita, P., ... Endsley, J. (2013). A Humanized Mouse Model of Tuberculosis. PLoS One, 8(5), [e63331]. https://doi.org/10.1371/journal.pone.0063331

A Humanized Mouse Model of Tuberculosis. / Calderon, Veronica E.; Valbuena, Gustavo; Goez, Yenny; Judy, Barbara M.; Huante, Matthew; Sutjita, Putri; Johnston, R. Katie; Estes, D. Mark; Hunter, Robert L.; Actor, Jeffrey K.; Cirillo, Jeffrey D.; Endsley, Janice.

In: PLoS One, Vol. 8, No. 5, e63331, 17.05.2013.

Research output: Contribution to journalArticle

Calderon, VE, Valbuena, G, Goez, Y, Judy, BM, Huante, M, Sutjita, P, Johnston, RK, Estes, DM, Hunter, RL, Actor, JK, Cirillo, JD & Endsley, J 2013, 'A Humanized Mouse Model of Tuberculosis', PLoS One, vol. 8, no. 5, e63331. https://doi.org/10.1371/journal.pone.0063331
Calderon VE, Valbuena G, Goez Y, Judy BM, Huante M, Sutjita P et al. A Humanized Mouse Model of Tuberculosis. PLoS One. 2013 May 17;8(5). e63331. https://doi.org/10.1371/journal.pone.0063331
Calderon, Veronica E. ; Valbuena, Gustavo ; Goez, Yenny ; Judy, Barbara M. ; Huante, Matthew ; Sutjita, Putri ; Johnston, R. Katie ; Estes, D. Mark ; Hunter, Robert L. ; Actor, Jeffrey K. ; Cirillo, Jeffrey D. ; Endsley, Janice. / A Humanized Mouse Model of Tuberculosis. In: PLoS One. 2013 ; Vol. 8, No. 5.
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