致病性结核分枝杆菌通过释放肿瘤坏死因子受体2（TNF-R2）逃避宿主巨噬细胞的凋亡，导致肿瘤坏死因子-α（TNF-α）失活。
Pathogenic Mycobacterium tuberculosis evades apoptosis of host macrophages by release of TNF-R2, resulting in inactivation of TNF-alpha.
作者信息
Balcewicz-Sablinska M K, Keane J, Kornfeld H, Remold H G
机构信息
Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
出版信息
J Immunol. 1998 Sep 1;161(5):2636-41.
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.
结核分枝杆菌（MTB）感染通过肿瘤坏死因子-α（TNF-α）依赖机制诱导人肺泡巨噬细胞（AMphi）凋亡。这种凋亡反应被认为是一种防御机制，可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，毒力强的MTB菌株H37Rv诱导的AMphi凋亡比减毒株H37Ra少得多。我们现在报告，用H37Rv或H37Ra感染AMphi，通过酶联免疫吸附测定法（ELISA）测得的TNF-α水平相当，但在H37Rv感染的AMphi上清液中，TNF-α生物活性降低。可溶性肿瘤坏死因子受体2（sTNFR2）的差异释放，以及无活性的TNF-α - TNFR2复合物的形成，解释了这些培养物中TNF-α生物活性的差异。H37Rv感染的AMphi释放sTNFR2依赖于白细胞介素-10（IL-10），因为它受到中和抗IL-10抗体的抑制。因此，毒力强的MTB可利用IL-10作为上游介质，调节感染后AMphi产生的TNF-α的作用。
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