Differentiation of monocytes to macrophages switches the Mycobacterium tuberculosis effect on HIV-1 replication from stimulation to inhibition:: Modulation of interferon response and CCAAT/enhancer binding protein β expression
Differentiation of monocytes to macrophages switches the Mycobacterium tuberculosis effect on HIV-1 replication from stimulation to inhibition:: Modulation of interferon response and CCAAT/enhancer binding protein β expression
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DOI：
10.4049/jimmunol.165.4.2028
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发表时间：
2000-08-15
影响因子：
4.4
通讯作者：
Pine, R
中科院分区：
文献类型：
--
作者：
Weiden, M;Tanaka, N;Pine, R
HIV-1复制在未发炎的肺巨噬细胞中被抑制，并在结核病期间被刺激，试图概括HIV-1复制在体外原代单核细胞和巨噬细胞以及在未经处理和PMA处理的THP-1细胞系体外模型中的激活情况，根据细胞的分化状态而产生相反的结果。单核细胞感染结核分枝杆菌后，可促进HIV-1复制并产生37 kDa CCAAT/增强子结合蛋白β(C/EBPβ)转录因子，而巨噬细胞抑制HIV-1复制并产生抑制16 kDa C/EBPβ转录因子。干扰素-β诱导巨噬细胞抑制16-kDa C/EBP-β，但不影响单核细胞C/EBP-β的表达。巨噬细胞能激活由STAT-1、STAT-2和IPN调节因子(IRF)-9组成的转录因子-3(ISGF-3)。感染结核分枝杆菌或用I型干扰素刺激后，巨噬细胞表达IRF-9 DNA结合活性，而单核细胞不表达，加入IRF-9组分后，单核细胞提取液中重组了ISGF-3。诱导分化时干扰素反应性的调节至少部分是通过转录后调节的IRF-9表达的增加来实现的，单核细胞和巨噬细胞都能维持干扰素的反应性，在干扰素刺激后激活STAT-1同源二聚体的形成和STAT-1基因的转录，此外，单核细胞和巨噬细胞在感染结核分枝杆菌后都能激活核因子-kappaB。这些结果表明，诱导ISGF-3，抑制16 kDa C/EBPβ的表达，以及通过转录机制抑制HIV-1复制是巨噬细胞对结核分枝杆菌感染的特异性反应。
HIV-1 replication is inhibited in uninflamed lung macrophages and is stimulated during tuberculosis, Attempts to recapitulate activation of HIV-1 replication in primary monocytes and macrophages ex vivo and in the untreated and PMA-treated THP-1 cell line model in vitro have produced opposite results depending on the state of differentiation of the cells. After infection with Mycobacterium tuberculosis, monocytes enhanced HIV-1 replication and produced a stimulatory 37-kDa CCAAT/enhancer binding protein beta (C/EBP beta) transcription factor, whereas macrophages suppressed HIV-1 replication and produced an inhibitory 16-kDa C/EBP beta transcription factor. IFN-beta induced inhibitory 16-kDa C/EBP beta in macrophages, but had no effect on C/EBP beta expression in monocytes, Macrophages, but not monocytes, were able to activate IFN-stimulated gene factor-3 (ISGF-3), a transcription factor composed of STAT-1, STAT-2, and IPN regulatory factor (IRF)-9, after infection with M. tuberculosis or stimulation with type I IFN, Macrophages expressed IRF-9 DNA-binding activity, but monocytes did not, and addition of the IRF-9 component reconstituted ISGF-3 in extracts of IFN-treated monocytes, Modulation of IFN responsiveness upon differentiation occurred at least in part through a post-transcriptionally regulated increase in IRF-9 expression, Both monocytes and macrophages maintained IFN responsiveness, activating STAT-1 homodimer formation and transcription of the STAT-1 gene after IFN stimulation, In addition, both monocytes and macrophages were able to activate NF-kappa B upon infection with M, tuberculosis. These results show that induction of ISGF-3, expression of the inhibitory 16-kDa C/EBP beta, and suppression of HIV-1 replication via a transcriptional mechanism are macrophage-specific responses to infection with M, tuberculosis.