Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5586963 | Cytokine | 2017 | 10 Pages |
Abstract
Infection with Mycobacterium tuberculosis (M.tb) is associated with increased deaths worldwide. Alveolar macrophages (AMs) play a critical role in host defense against infection with this pathogen. In this work we tested the hypothesis that passive transfer of normal AMs, IFN-γ activated AMs, or macrophages transduced to over-express IFN-γ into the lungs of immunosuppressed SCID mice, where resident macrophages are present but not functional, would enhance alveolar immunity and increase clearance of pulmonary M.tb infection. Accordingly, SCID mice were infected with M.tb intratracheally (I.T.), following which they received either control macrophages or macrophages overexpressing IFN-γ (J774A.1). The extent of M.tb infection was assessed at 30 days post-M.tb infection. SCID mice administered macrophages over-expressing IFN-γ showed a significant decrease in M.tb burden and increased survival compared to J774A.1 control macrophages or untreated mice. This was further associated with a significant increase in IFN-γ and TNF-α mRNA and protein expression, as well as NF-κB (p65) mRNA, in the lungs. The increase in IFN-γ and TNF-α lung levels was inversely proportional to the number of M.tb organisms recovered. These results provide evidence that administration of macrophages overexpressing IFN-γ inhibit M.tb growth in vivo and may enhance host defense against M.tb infection.
Keywords
NH4ClBALHBSSAMSRNISCIDDMEMCFUMDRM.tbKHCO3Dulbecco’s Minimum Essential MediumXDRNF-κBINF-γDiIROSEDTAEthylenediaminetetraacetic acidReconstitutionPotassium bicarbonateTuberculosistumor necrosis factor alphaLungTNF-αnuclear factor kappa Bbronchoalveolar lavageAlveolar macrophagesMycobacterium tuberculosisHanks’ balanced salt solutionExtensively drug resistantmulti-drug resistantcolony forming unitsreactive nitrogen intermediatesReactive oxygen intermediatesGene therapyAmmonium chlorideImmunodeficiencyInterferon gamma
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Authors
Rajamouli Pasula, William J. II, Banu Rekha Kesavalu, Maher Y. Abdalla, Bradley E. Britigan,