Passive transfer of interferon-γ over-expressing macrophages enhances resistance of SCID mice to Mycobacterium tuberculosis infection.
Passive transfer of interferon-γ over-expressing macrophages enhances resistance of SCID mice to Mycobacterium tuberculosis infection.
复制标题
干扰素γ过度表达巨噬细胞的被动转移增强了SCID小鼠对结核分枝杆菌感染的抵抗力。
DOI：
10.1016/j.cyto.2017.02.009
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发表时间：
2017
期刊：
影响因子：
3.8
通讯作者：
Britigan,BradleyE
中科院分区：
文献类型：
--
作者：
Pasula,Rajamouli;Martin2nd,WilliamJ;Kesavalu,BanuRekha;Abdalla,MaherY;Britigan,BradleyE
结核分枝杆菌（M.tb）感染与全世界死亡率的增加有关。肺泡巨噬细胞（AM）在宿主防御这种病原体感染中起着关键作用。在这项工作中，我们测试了这样一种假设，即正常AM、IFN-γ激活的AM或转导过表达IFN-γ的巨噬细胞被动转移到免疫抑制的SCID小鼠的肺中，其中存在常驻巨噬细胞但不起作用，将增强肺泡免疫并增加肺M. tbinfection的清除。因此，将SCID小鼠用结核分枝杆菌感染，随后它们接受对照巨噬细胞或过表达IFN-γ的巨噬细胞（J774A.1）。在M. t感染后30天评估M. t感染的程度。与J774A.1对照巨噬细胞或未处理的小鼠相比，给予过表达IFN-γ的巨噬细胞的SCID小鼠显示出M. tb负荷的显著降低和存活率的增加。这进一步与肺中IFN-γ和TNF-α mRNA和蛋白表达以及NF-κB（p65）mRNA的显著增加相关。IFN-γ和TNF-α肺水平的增加与回收的结核分枝杆菌数量成反比。这些结果提供了证据表明，给予体内过表达IFN-γ的巨噬细胞可促进结核分枝杆菌的生长，并可增强宿主对结核分枝杆菌感染的防御。
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 pulmonaryM.tbinfection. Accordingly, SCID mice were infected withM.tbintratracheally (I.T.), following which they received either control macrophages or macrophages overexpressing IFN-γ (J774A.1). The extent ofM.tbinfection was assessed at 30 days post-M.tbinfection. SCID mice administered macrophages over-expressing IFN-γ showed a significant decrease inM.tbburden 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 ofM.tborganisms recovered. These results provide evidence that administration of macrophages overexpressing IFN-γ inhibitM.tbgrowthin vivoand may enhance host defense againstM.tbinfection.