Mycobacterium bovis BCG vaccination modulates TNF-alpha production after pulmonary challenge with virulent Mycobacterium tuberculosis in guinea pigs.
Tumor necrosis factor-alpha (TNF-alpha) plays critical and opposing roles in the pathogenesis of tuberculosis (TB). We examined the effects of Mycobacterium bovis BCG vaccination on TNF-alpha production in three distinct guinea pig leukocyte populations before and after pulmonary infection with M. tuberculosis H37Rv. Following BCG vaccination alone, and following challenge, bronchoalveolar lavage cells (BALC), resident peritoneal cells (PC), and splenocytes (SPC) were stimulated with purified protein derivative (PPD). Before virulent challenge, BCG vaccination clearly enhanced the ability of BALC, PC and SPC to produce TNF-alpha in response to PPD stimulation ex vivo. Following challenge, the TNF-alpha production of all three leukocyte populations from BCG-vaccinated animals remained relatively constant at pre-challenged levels. In sharp contrast, 5 weeks post-challenge, all three leukocyte populations from unvaccinated animals produced very high amounts of TNF-alpha in response to PPD. Three weeks post-challenge, SPC from one of the unvaccinated animals produced higher levels of TNF-alpha but the others produced lower levels of TNF-alpha than BCG-vaccinated animals. As expected, BCG vaccination reduced the levels of virulent mycobacteria in both the lungs and spleens. Thus, BCG vaccination allows guinea pigs to modulate TNF-alpha levels in conjunction with a reduction in bacillary loads in their tissues.
Yamamoto
Toshiko
T
Department of Microbial and Molecular Pathogenesis, The Texas A&M University System Health Science Center, College Station, TX 77843-1114, USA.
Lasco
Todd M
TM
Uchida
Kazuyuki
K
Goto
Yoshitaka
Y
Jeevan
Amminikutty
A
McFarland
Christine
C
Ly
Lan
L
Yamamoto
Saburo
S
McMurray
David N
DN
D000336:Aerosols; D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D006168:Guinea Pigs; D007962:Leukocytes / Q000276:immunology; D008168:Lung / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010529:Peritoneal Cavity / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014373:Tuberculin / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D014774:Virulence
D000336:Aerosols; D001500:BCG Vaccine; D014373:Tuberculin; D014409:Tumor Necrosis Factor-alpha