Figure 6.

Adenovirus encoding granulocyte–macrophage colony-stimulating factor (AdGM-CSF) treatment prevents reactivation of chronic tuberculosis (TB) similar to latent infection following immunosuppression and prevention of transmission in co-housed healthy mice. (a) Mice were infected with low-dose Mycobacterium tuberculosis (Mtb) H37Rv to induce chronic infection similar to latent infection, and after 7 months animals were treated with AdGM-CSF (black bars) or Addl70-3 (white bars); after 1 month mice were treated with cortisone for 1 month to induce disease reactivation. Animals treated with AdGM-CSF showed lower pulmonary bacilli loads and (b) lesser tissue damage (pneumonia) than mice treated with Addl70-3. (c) With regard to evaluation of the effect of AdGM-CSF treatment in the prevention of transmission, groups of mice were infected with mild virulent Mtb strain H37Rv or (d) with the highly virulent Beijing strain 9001000 and co-housed with healthy mice treated with isoniazid (INH; hatched bar), AdGM-CSF (black bar) or Addl70-3(white bar) for 2 months; the lungs were used for bacilli burden determination by quantification of colony-forming units (CFUs). In comparison with animals treated with Addl70-3, the lungs of animals treated with INH or AdGM-CSF do not show bacilli growth. (e) Significantly lower delayed-type hypersensitivity (DTH) was measured in animals treated with INH or AdGM-CSF than mice treated with Addl70-3 that were co-housed with mice infected with Mtb strain H37Rv. (f) In contrast, there was no DTH difference in animals treated with INH or Addl70-3 when co-housed with mice infected with highly virulent Beijing strain, while animals treated with AdGM-CSF showed significantly lower DTH. All values are means ± standard deviation (s.d.) from two independent experiments with five mice per group;*P < 0·05 (561 × 632 mm; 200 × 200 DPI).