title: Interferon-alphabeta mediates partial control of early pulmonary Mycobacterium bovis bacillus Calmette-Guérin infection.
abstract: The role of type I interferon (IFN-alphabeta) in modulating innate or adaptive immune responses against mycobacterial infection in the lung is unclear. In this study we investigated the susceptibility of IFN-alphabeta-receptor-deficient (IFN-alphabetaR-/-) mice to pulmonary infection with aerosolized Mycobacterium bovis bacillus Calmette-Guérin (BCG). During early infection (2-3 weeks), enhanced growth of BCG was measured in the lungs of IFN-alphabetaR-/- mice compared to wild-type mice. However, during late infection the burden of BCG was similar in the lungs of IFN-alphabetaR-/- and wild-type mice. Although control of BCG growth was delayed, recruitment and activation of T and natural killer cells, production of IFN-gamma, and cytokine expression were all similar in wild-type and IFN-alphabetaR-/- mice. However, decreased expression of nitric oxide in bronchoalveolar lavage fluids from IFN-alphabetaR-/- mice correlated with enhanced growth of BCG. Bone marrow-derived macrophages from IFN-alphabetaR-/- mice also produced less nitric oxide following infection with BCG in vitro. These findings suggest that IFN-alphabeta contributes to innate immunity to pulmonary mycobacterial infection by augmenting production of nitric oxide.
authors.affiliation: Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4984, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kuchtey
authors.forename: Scott A
authors.initials: SA
authors.lastname: Fulton
authors.forename: Scott M
authors.initials: SM
authors.lastname: Reba
authors.forename: Clifford V
authors.initials: CV
authors.lastname: Harding
authors.forename: W Henry
authors.initials: WH
authors.lastname: Boom
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000254:growth & development; D009569:Nitric Oxide / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000172:deficiency / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control
chemical_list: D008565:Membrane Proteins; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D009569:Nitric Oxide; D007371:Interferon-gamma