Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions

Jamie Harper, Ciaran Skerry, Stephanie L. Davis, Rokeya Tasneen, Mariah Weir, Igor Kramnik, William Ramses Bishai, Martin Gilbert Pomper, Eric Nuermberger, Sanjay Jain

Research output: Contribution to journalArticle

Abstract

Background.Preclinical evaluation of tuberculosis drugs is generally limited to mice. However, necrosis and hypoxia, key features of human tuberculosis lesions, are lacking in conventional mouse strains.Methods.We used C3HeB/FeJ mice, which develop necrotic lesions in response to Mycobacterium tuberculosis infection. Positron emission tomography in live infected animals, postmortem pimonidazole immunohistochemistry, and bacterial gene expression analyses were used to assess whether tuberculosis lesions in C3HeB/FeJ are hypoxic. Efficacy of combination drug treatment, including PA-824, active against M. tuberculosis under hypoxic conditions, was also evaluated.Results. Tuberculosis lesions in C3HeB/FeJ (but not BALB/c) were found to be hypoxic and associated with up-regulation of known hypoxia-associated bacterial genes (P

Original languageEnglish (US)
Pages (from-to)595-602
Number of pages8
JournalJournal of Infectious Diseases
Volume205
Issue number4
DOIs
StatePublished - Feb 15 2012

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Granuloma
Tuberculosis
Bacterial Genes
Mycobacterium tuberculosis
Preclinical Drug Evaluations
Mycobacterium Infections
Drug Combinations
Positron-Emission Tomography
Necrosis
Up-Regulation
Immunohistochemistry
Gene Expression
Hypoxia
Therapeutics

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Harper, J., Skerry, C., Davis, S. L., Tasneen, R., Weir, M., Kramnik, I., ... Jain, S. (2012). Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions. Journal of Infectious Diseases, 205(4), 595-602. https://doi.org/10.1093/infdis/jir786

Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions. / Harper, Jamie; Skerry, Ciaran; Davis, Stephanie L.; Tasneen, Rokeya; Weir, Mariah; Kramnik, Igor; Bishai, William Ramses; Pomper, Martin Gilbert; Nuermberger, Eric; Jain, Sanjay.

In: Journal of Infectious Diseases, Vol. 205, No. 4, 15.02.2012, p. 595-602.

Research output: Contribution to journalArticle

Harper J, Skerry C, Davis SL, Tasneen R, Weir M, Kramnik I et al. Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions. Journal of Infectious Diseases. 2012 Feb 15;205(4):595-602. https://doi.org/10.1093/infdis/jir786
Harper, Jamie ; Skerry, Ciaran ; Davis, Stephanie L. ; Tasneen, Rokeya ; Weir, Mariah ; Kramnik, Igor ; Bishai, William Ramses ; Pomper, Martin Gilbert ; Nuermberger, Eric ; Jain, Sanjay. / Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions. In: Journal of Infectious Diseases. 2012 ; Vol. 205, No. 4. pp. 595-602.
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