Alpha/beta interferon impairs the ability of human macrophages to control growth of Mycobacterium bovis BCG
Alpha/beta interferon impairs the ability of human macrophages to control growth of Mycobacterium bovis BCG
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DOI：
10.1128/iai.70.6.3020-3025.2002
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发表时间：
2002-06-01
影响因子：
3.1
通讯作者：
Hance, AJ
中科院分区：
文献类型：
--
作者：
Bouchonnet, F;Boechat, N;Hance, AJ
已显示，对感染结核分枝杆菌的小鼠施用α/β干扰素（IFN-α/β）可增加分枝杆菌生长。由于IFN-α/β对巨噬细胞的分化和功能活性具有直接的多效性作用，我们评估了IFN-α/β对体外人单核细胞/巨噬细胞中分枝杆菌生长的影响。在最佳细胞密度下培养的单核细胞可以控制M.牛BCG，如通过测量由分枝杆菌报告菌株表达的荧光素酶活性和通过计数CFU两者评估的。相比之下，当单核细胞在感染前3天或感染同时用α干扰素（IFN-α）处理时，观察到分枝杆菌生长不受限制。在IFN-α和IFN-β中观察到这种显著的抑制分枝杆菌活性的丧失，并且在新鲜分离的单核细胞和培养物衍生的巨噬细胞中诱导。用IFN-α预处理单核细胞改变了细胞形态，降低了培养后的存活率，但对培养衍生的巨噬细胞也没有观察到，这表明IFN-α对分枝杆菌抑制活性和细胞分化和死亡的影响可以分离。这些结果与IFN-α/β的分泌可能直接促进携带这些生物体的患者中的分枝杆菌生长的可能性相一致。
Administration of alpha/beta interferon (IFN-alpha/beta) to mice infected with Mycobacterium tuberculosis has been shown to increase mycobacterial growth. Because IFN-alpha/beta has direct pleiotropic effects on the differentiation and functional activities of macrophages, we evaluated the effect of IFN-alpha/beta on mycobacterial growth in human monocytes/macrophages in vitro. Monocytes cultured at optimal cell density could control the growth of M. bovis BCG, as assessed both by measurement of luciferase activity expressed by a mycobacterial reporter strain and by counting of CFU. In contrast, unrestrained mycobacterial growth was observed when monocytes were treated with alpha interferon (IFN-alpha) 3 days prior to or concomitant with infection. This striking loss of mycobacteriostatic activity was observed with IFN-alpha and IFN-beta and was induced in both freshly isolated monocytes and culture-derived macrophages. Pretreatment of monocytes with IFN-alpha modified cellular morphology and reduced viability following culture, but neither was observed for culture-derived macrophages, indicating that the effects of IFN-alpha on mycobacteriostatic activity and cell differentiation and death could be dissociated. These results are compatible with the possibility that the secretion of IFN-alpha/beta could directly promote mycobacterial growth in patients harboring these organisms.