Spectrum of manifestations of Mycobacterium tuberculosis infection in primates infected with SIV

AIDS Res Hum Retroviruses. 2003 Jul;19(7):585-95. doi: 10.1089/088922203322230950.

Abstract

To characterize the manifestations of coinfection with M. tuberculosis and SIV infection, we studied 12 SIV-infected rhesus monkeys, six of which were infected intrabronchially with a low dose of Mycobacterium tuberculosis H37Rv. In the six coinfected animals, M. tuberculosis antigen-stimulated lung and blood cells produced high concentrations of IFN-gamma but not IL-4 8-16 weeks after infection. Of the three coinfected animals with high levels of plasma viremia, two developed disseminated tuberculosis and the other died of bacterial peritonitis. Of three coinfected animals with moderate levels of plasma viremia, two had no clinical or radiographic evidence of tuberculosis or progressive SIV infection for 6 months after infection. At neuropsy, pulmonary granulomata were observed and acid-fast organisms or M. tuberculosis were present. These clinical, immunologic and pathologic findings are consistent with those in humans with latent tuberculosis infection (LTBI), and suggest that a model of LTBI in SIV-infected primates can be developed. Such a model will permit delineation of the immunologic and microbial factors that characterize LTBI in HIV-infected persons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Disease Models, Animal
  • Feasibility Studies
  • Female
  • Gene Expression Regulation
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Leukocytes, Mononuclear / metabolism
  • Lung / pathology
  • Macaca mulatta
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Simian Acquired Immunodeficiency Syndrome / complications*
  • Tuberculoma / pathology
  • Tuberculosis, Miliary / complications
  • Tuberculosis, Miliary / immunology
  • Tuberculosis, Miliary / pathology
  • Tuberculosis, Pulmonary / complications*
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / pathology
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Viral Load
  • Viremia / complications
  • Weight Loss

Substances

  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-4
  • Interferon-gamma