期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 39, 期 7, 页码 1914-1922出版社
WILEY
DOI: 10.1002/eji.200839115
关键词
Cytokines; Infections; bacterial; Inflammation
类别
资金
- Top Institute Pharma consortium [D1-101]
- Netherlands Organization of Scientific Research
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.
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