Pathogenic Mycobacterium tuberculosis evades apoptosis of host macrophages by release of TNF-R2, resulting in inactivation of TNF-alpha.
Pathogenic Mycobacterium tuberculosis evades apoptosis of host macrophages by release of TNF-R2, resulting in inactivation of TNF-alpha.
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DOI：
10.4049/jimmunol.161.5.2636
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发表时间：
1998-09
影响因子：
4.4
通讯作者：
M. K. Balcewicz-Sablinska;Joseph Keane;H. Kornfeld;H. Remold
中科院分区：
文献类型：
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作者：
M. K. Balcewicz-Sablinska;Joseph Keane;H. Kornfeld;H. Remold
结核分枝杆菌（MTB）感染通过TNF-α依赖性机制诱导人肺泡巨噬细胞（AMphi）凋亡。凋亡反应被假定为一种防御机制，限制这种细胞内病原体的生长。与该模型一致，最近的研究表明，毒性MTB菌株H37 Rv诱导的AMphi细胞凋亡比减毒株H37 Ra少得多。我们现在报道，用H37 Rv或H37 Ra感染AMphi诱导通过ELISA测量的相当水平的TNF-α，但是TNF-α生物活性在H37 Rv感染的AMphi的上清液中降低。可溶性TNFR 2（sTNFR 2）的差异释放以及无活性TNF-α-TNFR 2复合物的形成解释了这些培养物中TNF-α生物活性的差异。H37 Rv感染的AMphi释放sTNFR 2是IL-10依赖性的，因为它被中和性抗IL-10 Ab抑制。因此，感染后AMphi产生的TNF-α的作用可以通过毒性MTB调节，使用IL-10作为上游介质。
Infection by Mycobacterium tuberculosis (MTB) induces human alveolar macrophage (AMphi) apoptosis by a TNF-alpha-dependent mechanism. The apoptotic response is postulated to be a defense mechanism, limiting the growth of this intracellular pathogen. Consistent with that model, recent studies showed that the virulent MTB strain H37Rv induces substantially less AMphi apoptosis than the attenuated strain H37Ra. We now report that AMphi infection with either H37Rv or H37Ra induces comparable levels of TNF-alpha measured by ELISA but that TNF-alpha bioactivity is reduced in supernatants of H37Rv-infected AMphi. Differential release of soluble TNFR2 (sTNFR2), with formation of inactive TNF-alpha-TNFR2 complexes accounted for the difference in TNF-alpha bioactivity in these cultures. Release of sTNFR2 by H37Rv-infected AMphi was IL-10 dependent since it was inhibited by neutralizing anti-IL-10 Ab. Thus, the effect of TNF-alpha produced by AMphi following infection can be modulated by virulent MTB, using IL-10 as an upstream mediator.