Interferon-αβ mediates partial control of early pulmonary Mycobacterium bovis bacillus Calmette-Guerin infection

The role of type I interferon (IFN-alpha beta) in modulating innate or adaptive immune responses against mycobacterial infection in the lung is unclear. In this study we investigated the susceptibility of IFN-alpha beta-receptor-deficient (IFN-alpha beta R-/-) mice to pulmonary infection with aerosolized Mycobacterium bovis bacillus Calmette-Guerin (BCG). During early infection (2-3 weeks), enhanced growth of BCG was measured in the lungs of IFN-alpha beta R-/- mice compared to wild-type mice. However, during late infection the burden of BCG was similar in the lungs of IFN-alpha beta R-/- 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-alpha beta R-/- mice. However, decreased expression of nitric oxide in bronchoalveolar lavage fluids from IFN-alpha beta R-/- mice correlated with enhanced growth of BCG. Bone marrow-derived macrophages from IFN-alpha beta R-/- mice also produced less nitric oxide following infection with BCG in vitro. These findings suggest that IFN-alpha beta contributes to innate immunity to pulmonary mycobacterial infection by augmenting production of nitric oxide.