High resolution radiographic and fine immunologic definition of TB disease progression in the rhesus macaque

David M. Lewinsohn, Ian S. Tydeman, Marisa Frieder, Jeff E. Grotzke, Rebecca A. Lines, Sheela Ahmed, Kamm D. Prongay, Steven L. Primack, Lois M.A. Colgin, Anne D. Lewis, Deborah A. Lewinsohn

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Mycobacterium tuberculosis infection in non-human primates parallels human tuberculosis, and provides a valuable vaccine evaluation model. However, this model is limited by the availability of real-time, non-invasive information regarding disease progression. Consequently, we have combined computed tomography scanning with enumeration of antigen-specific T cell responses. Four rhesus monkeys were infected with M. tuberculosis strain H37Rv (1000 cfu) in the right lower lobe via a bronchoscope. All uniformly developed progressive tuberculosis, and required euthanasia at 12 weeks. Computed tomography scanning provided detailed real-time imaging of disease progression. At necropsy, computed tomography and pathohistologic findings were tightly correlated, and characteristic of human disease. Immunologic monitoring demonstrated progressive evolution of high frequency M. tuberculosis-specific CD4+ and CD8+ T cell responses. Peripheral blood effector cell frequencies were similar to those observed in tissues. In summary, computed tomography scanning in conjunction with immunologic monitoring provides a non-invasive, accurate, and rapid assessment of tuberculosis in the non-human primate.

Original languageEnglish (US)
Pages (from-to)2587-2598
Number of pages12
JournalMicrobes and Infection
Volume8
Issue number11
DOIs
StatePublished - Sep 2006

Keywords

  • CT scanning
  • Macaque
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Infectious Diseases

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