Stereological analysis of bacterial load and lung lesions in nonhuman primates (rhesus macaques) experimentally infected with Mycobacterium tuberculosis

Paul A Luciw, Karen L. Oslund, Xiao Wei Yang, Lourdes Adamson, Resmi Ravindran, Don R. Canfield, Ross Tarara, Linda Hirst, Miles Christensen, Nicholas W. Lerche, Heather Offenstein, David Lewinsohn, Frank Ventimiglia, Laurie Brignolo, Erik R Wisner, Dallas M. Hyde

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Infection with Mycobacterium tuberculosis primarily produces a multifocal distribution of pulmonary granulomas in which the pathogen resides. Accordingly, quantitative assessment of the bacterial load and pathology is a substantial challenge in tuberculosis. Such assessments are critical for studies of the pathogenesis and for the development of vaccines and drugs in animal models of experimental M. tuberculosis infection. Stereology enables unbiased quantitation of three-dimensional objects from two-dimensional sections and thus is suited to quantify histological lesions. We have developed a protocol for stereological analysis of the lung in rhesus macaques inoculated with a pathogenic clinical strain of M. tuberculosis (Erdman strain). These animals exhibit a pattern of infection and tuberculosis similar to that of naturally infected humans. Conditions were optimized for collecting lung samples in a nonbiased, random manner. Bacterial load in these samples was assessed by a standard plating assay, and granulomas were graded and enumerated microscopically. Stereological analysis provided quantitative data that supported a significant correlation between bacterial load and lung granulomas. Thus this stereological approach enables a quantitative, statistically valid analysis of the impact of M. tuberculosis infection in the lung and will serve as an essential tool for objectively comparing the efficacy of drugs and vaccines.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume301
Issue number5
DOIs
StatePublished - Nov 2011

Keywords

  • Granuloma
  • Morphometry
  • Quantitative pathology

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

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    Luciw, P. A., Oslund, K. L., Yang, X. W., Adamson, L., Ravindran, R., Canfield, D. R., Tarara, R., Hirst, L., Christensen, M., Lerche, N. W., Offenstein, H., Lewinsohn, D., Ventimiglia, F., Brignolo, L., Wisner, E. R., & Hyde, D. M. (2011). Stereological analysis of bacterial load and lung lesions in nonhuman primates (rhesus macaques) experimentally infected with Mycobacterium tuberculosis. American Journal of Physiology - Lung Cellular and Molecular Physiology, 301(5). https://doi.org/10.1152/ajplung.00120.2011