Kuchtey John, Fulton Scott A, Reba Scott M, Harding Clifford V, Boom W Henry
Institute of Pathology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106-4984, USA.
Immunology. 2006 May;118(1):39-49. doi: 10.1111/j.1365-2567.2006.02337.x.
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.
I型干扰素（IFN-αβ）在调节针对肺部分枝杆菌感染的固有免疫或适应性免疫反应中的作用尚不清楚。在本研究中，我们调查了I型干扰素受体缺陷（IFN-αβR-/-）小鼠对雾化卡介苗（BCG）肺部感染的易感性。在早期感染（2-3周）期间，与野生型小鼠相比，IFN-αβR-/-小鼠肺部的卡介苗生长增强。然而，在晚期感染期间，IFN-αβR-/-和野生型小鼠肺部的卡介苗负担相似。尽管卡介苗生长的控制有所延迟，但野生型和IFN-αβR-/-小鼠中T细胞和自然杀伤细胞的募集与激活、IFN-γ的产生以及细胞因子表达均相似。然而，IFN-αβR-/-小鼠支气管肺泡灌洗液中一氧化氮表达的降低与卡介苗生长的增强相关。IFN-αβR-/-小鼠骨髓来源的巨噬细胞在体外感染卡介苗后也产生较少的一氧化氮。这些发现表明，IFN-αβ通过增加一氧化氮的产生来促进对肺部分枝杆菌感染的固有免疫。
