Evidence for a rhesus monkey model of asymptomatic tuberculosis

J Med Primatol. 2004 Jun;33(3):134-45. doi: 10.1111/j.1600-0684.2004.00062.x.

Abstract

Rhesus monkeys (RM) were inoculated intrabronchially with graded doses of Mycobacterium tuberculosis (MTB) strains Erdman and H37Rv in an effort to produce a model of asymptomatic tuberculosis infection. Erdman strain produced active disease within 7-11 weeks regardless of dose. Low doses of H37Rv resulted in asymptomatic infections; high doses produced active disease within 11 weeks. Over a 4-month period of post-inoculation study, MTB culture-filtrate protein (CFP)-stimulated bronchoalveolar lavage cells (BALC) and blood mononuclear cells (PBMC) from monkeys with active disease (30 cfu Erdman-inoculated) or asymptomatic infection (200 cfu H37Rv-inoculated) produced similar significant quantities of mRNA encoding for IFN-gamma or TNF-alpha, but insignificant quantities of IL-4 mRNA. Differences were observed in antigen-induced in vitro blastogenic responses and serum anti-lipoarabinomannan (LAM) antibody responses in animals with active compared with asymptomatic MTB infections. The results indicate that RM are a good model for the study of asymptomatic tuberculosis infections using low doses of H37Rv.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Body Burden
  • Bronchoalveolar Lavage Fluid / cytology
  • Cytokines / genetics
  • DNA / genetics
  • DNA Primers
  • Disease Models, Animal*
  • Electrophoresis, Agar Gel
  • Enzyme-Linked Immunosorbent Assay
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Immunohistochemistry
  • Immunosuppression Therapy
  • Leukocytes, Mononuclear / immunology
  • Lipopolysaccharides / immunology
  • Lymphocyte Activation / immunology
  • Macaca mulatta*
  • Microscopy, Confocal
  • Mycobacterium tuberculosis / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors
  • Tuberculosis / immunology*
  • Tuberculosis / pathology*

Substances

  • Cytokines
  • DNA Primers
  • Immunoglobulin G
  • Immunoglobulin M
  • Lipopolysaccharides
  • RNA, Messenger
  • lipoarabinomannan
  • DNA