Factors associated with severe granulomatous pneumonia in Mycobacterium tuberculosis-infected mice vaccinated therapeutically with hsp65 DNA

Infect Immun. 2005 Aug;73(8):5189-93. doi: 10.1128/IAI.73.8.5189-5193.2005.

Abstract

Resistant C57BL/6 mice infected in the lungs with Mycobacterium tuberculosis and then therapeutically vaccinated with Mycobacterium leprae-derived hsp65 DNA develop severe granulomatous pneumonia and tissue damage. Analysis of cells accumulating in the lungs of these animals revealed substantial increases in T cells secreting tumor necrosis factor alpha and CD8 cells staining positive for granzyme B. Stimulation of lung cells ex vivo revealed very high levels of interleukin-10, some of which was produced by B-1 B cells. This was probably an anti-inflammatory response, since lung pathology was dramatically worsened in B-cell gene-disrupted mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Chaperonin 60
  • Chaperonins / genetics*
  • DNA / therapeutic use*
  • Female
  • Immunohistochemistry
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mycobacterium leprae / genetics
  • Mycobacterium leprae / immunology
  • Mycobacterium tuberculosis / immunology
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / immunology
  • Tuberculosis, Pulmonary / microbiology

Substances

  • Bacterial Proteins
  • Chaperonin 60
  • heat-shock protein 65, Mycobacterium
  • DNA
  • Chaperonins