G Dai1, D N McMurray. 1. Department of Medical Microbiology and Immunology, College of Medicine, Texas A&M University System Health Science Center 77843-1114, USA.
Abstract
SETTING: TGF-beta 1 has been implicated as an important mediator of immuno-suppression in clinical tuberculosis. OBJECTIVE: The objective was to determine the role of TGF-beta 1 in experimental pulmonary tuberculosis in the guinea pig. DESIGN: Groups of guinea pigs, maintained on either a low protein (LP) diet or an isocaloric high protein (HP) diet, were challenged via the respiratory route with virulent Mycobacterium tuberculosis H37Rv. Ten days post-infection, guinea pigs were given daily intraperitoneal injections of recombinant human TGF-beta 1 (rhTGF-beta 1 tau for 10 consecutive days). Following the treatment, guinea pigs were euthanized, and PPD-induced proliferation of peripheral blood mononuclear cells (PBMCs) was assessed and disease resistance measured by recovery of mycobacteria from the lungs and spleens. In a second set of experiments, groups of HP and LP guinea pigs were vaccinated with attenuated M. tuberculosis H37Ra. Six weeks later, the effects of rhTGF-beta 1 on lymphoproliferation and cytokine production were determined. RESULTS: Protein deficiency significantly impaired host anti-tuberculosis resistance, as expected. Treatment with rhTGF-beta 1 significantly increased mycobacterial loads in the tissues of guinea pigs and decreased the PPD-induced proliferation of PBMCs from both LP and HP guinea pigs. PPD-driven lymphoproliferation, TNF-alpha and IFN production were significantly suppressed in vaccinated, protein-deficient guinea pigs, and rhTGF-beta 1 further inhibited lymphoproliferation and cytokine production. CONCLUSION: Both in vivo and in vitro results indicate that TGF-beta 1 exerts immunosuppressive activity and exacerbates the progression of experimental pulmonary tuberculosis in both normally nourished and protein-deficient guinea pigs.
SETTING:TGF-beta 1 has been implicated as an important mediator of immuno-suppression in clinical tuberculosis. OBJECTIVE: The objective was to determine the role of TGF-beta 1 in experimental pulmonary tuberculosis in the guinea pig. DESIGN: Groups of guinea pigs, maintained on either a low protein (LP) diet or an isocaloric high protein (HP) diet, were challenged via the respiratory route with virulent Mycobacterium tuberculosis H37Rv. Ten days post-infection, guinea pigs were given daily intraperitoneal injections of recombinant humanTGF-beta 1 (rhTGF-beta 1 tau for 10 consecutive days). Following the treatment, guinea pigs were euthanized, and PPD-induced proliferation of peripheral blood mononuclear cells (PBMCs) was assessed and disease resistance measured by recovery of mycobacteria from the lungs and spleens. In a second set of experiments, groups of HP and LP guinea pigs were vaccinated with attenuated M. tuberculosis H37Ra. Six weeks later, the effects of rhTGF-beta 1 on lymphoproliferation and cytokine production were determined. RESULTS:Protein deficiency significantly impaired host anti-tuberculosis resistance, as expected. Treatment with rhTGF-beta 1 significantly increased mycobacterial loads in the tissues of guinea pigs and decreased the PPD-induced proliferation of PBMCs from both LP and HP guinea pigs. PPD-driven lymphoproliferation, TNF-alpha and IFN production were significantly suppressed in vaccinated, protein-deficient guinea pigs, and rhTGF-beta 1 further inhibited lymphoproliferation and cytokine production. CONCLUSION: Both in vivo and in vitro results indicate that TGF-beta 1 exerts immunosuppressive activity and exacerbates the progression of experimental pulmonary tuberculosis in both normally nourished and protein-deficient guinea pigs.
Authors: K A Wilkinson; T D Martin; S M Reba; H Aung; R W Redline; W H Boom; Z Toossi; S A Fulton Journal: Infect Immun Date: 2000-11 Impact factor: 3.441
Authors: Andre Bafica; Charles A Scanga; Charles Serhan; Fabiana Machado; Sandy White; Alan Sher; Julio Aliberti Journal: J Clin Invest Date: 2005-06 Impact factor: 14.808