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

Authors

  • A. Francisco-Cruz,

    1. Section of Experimental Pathology, Department of Pathology, National Institute of Medical Sciences and Nutrition ‘Salvador Zubirán’
    2. Department of Immunology, National School of Biological Sciences, National Polytechnic Institute, DF, Mexico City, Mexico
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  • D. Mata-Espinosa,

    1. Section of Experimental Pathology, Department of Pathology, National Institute of Medical Sciences and Nutrition ‘Salvador Zubirán’
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  • S. Estrada-Parra,

    1. Department of Immunology, National School of Biological Sciences, National Polytechnic Institute, DF, Mexico City, Mexico
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  • Z. Xing,

    1. McMaster Immunology Research Centre, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
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  • R. Hernández-Pando

    Corresponding author
    • Section of Experimental Pathology, Department of Pathology, National Institute of Medical Sciences and Nutrition ‘Salvador Zubirán’
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Correspondence: R. Hernández-Pando, Section of Experimental Pathology, Department of Pathology, National Institute of Medical Sciences and Nutrition ‘Salvador Zubirán’, DF Mexico City14000, Mexico.

E-mail: rhpando@quetzal.innsz.mx; rhdezpando@hotmail.com

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.

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