Immunotherapeutic effects of recombinant adenovirus encoding granulocyte–macrophage colony‐stimulating factor in experimental pulmonary tuberculosis

Summary BALB /c mice with pulmonary tuberculosis ( TB ) develop a T helper cell type 1 that temporarily controls bacterial growth. Bacterial proliferation increases, accompanied by decreasing expression of interferon ( IFN )‐γ, tumour necrosis factor ( TNF )‐α and inducible nitric oxide synthase ( iNOS ). Activation of dendritic cells ( DCs ) is delayed. Intratracheal administration of only one dose of recombinant adenoviruses encoding granulocyte–macrophage colony‐stimulating factor ( AdGM ‐ CSF ) 1 day before Mycobacterium  tuberculosis ( Mtb ) infection produced a significant decrease of pulmonary bacterial loads, higher activated DCs and increased expression of TNF ‐α, IFN ‐γ and iNOS . When AdGM ‐ CSF was given in female mice B6D2F1 ( C57BL / 6J X DBA / 2J ) infected with a low Mtb dose to induce chronic infection similar to latent infection and corticosterone was used to induce reactivation, a very low bacilli burden in lungs was detected, and the same effect was observed in healthy mice co‐housed with mice infected with mild and highly virulent bacteria in a model of transmissibility. Thus, GM‐CSF is a significant cytokine in the immune protection against Mtb and gene therapy with AdGM ‐ CSF increased protective immunity when administered in a single dose 1 day before Mtb infection in a model of progressive disease, and when used to prevent reactivation of latent infection or transmission.