Transcriptional and inflammasome-mediated pathways for the induction of IL-1β production by Mycobacterium tuberculosis
Transcriptional and inflammasome-mediated pathways for the induction of IL-1β production by Mycobacterium tuberculosis
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DOI：
10.1002/eji.200839115
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发表时间：
2009-07-01
影响因子：
5.4
通讯作者：
Netea, Mihai G.
中科院分区：
文献类型：
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作者：
Kleinnijenhuis, Johanneke;Joosten, Leo A. B.;Netea, Mihai G.
IL-1家族的促炎细胞因子在抗分枝杆菌宿主防御机制中发挥重要作用。在本研究中，我们已经破译了从识别结核分枝杆菌到产生和释放IL-1 β（IL-1家族中最重要的成员）的途径。通过刺激各种模式识别受体缺陷的细胞，我们可以证明IL-1 β的产生是由M。结核病通过涉及TLR 2/TLR 6和NOD 2受体的途径。相反，TLR 4、TLR 9和TLR 1受体不参与IL-1 β诱导。对M. TLR和NOD 2引起的结核病通过涉及ERK、p38和Rip 2的机制而非JNK导致proIL-1 β的转录。有趣的是，虽然胱天蛋白酶-1对于proIL-1 β的加工是必需的，但胱天蛋白酶-1的活化并不依赖于M对细胞的刺激。结核单核细胞表达组成型活性caspase-1。IL-1 β的分泌依赖于内源性释放的ATP对P2 X7诱导途径的激活。总之，我们已经剖析了M.结核，这可能有助于更深入地了解M.结核
Proinflammatory cytokines of the IL-1 family play an important role for the anti-mycobacterial host defense mechanisms. In the present study we have deciphered the pathways leading from recognition of Mycobacterium tuberculosis to the production and release of IL-1 beta, the most important member of the IL-1 family. By stimulating cells defective in various pattern recognition receptors, we could demonstrate that IL-1 beta production is induced by M. tuberculosis through pathways involving TLR2/TLR6 and NOD2 receptors. In contrast, TLR4, TLR9 and TLR1 receptors are not involved in IL-1 beta induction. Recognition of M. tuberculosis by TLR and NOD2 leads to transcription of proIL-1 beta through mechanisms involving ERK, p38 and Rip2, but not JNK. interestingly, although caspase-1 is necessary for the processing of proIL-1 beta, activation of caspase-1 is not dependent on the stimulation of cells by M. tuberculosis. Monocytes expressed constitutively active caspase-1. The secretion of IL-1 beta is dependent on the activation of P2X7-induced pathways by endogenously released ATP. In conclusion, we have dissected the molecular mechanisms responsible for IL-1 beta production by M. tuberculosis, and that may contribute to a deeper knowledge of the mechanisms of cell activation by M. tuberculosis.