IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities (Nat Med, 2007, 13:927-934)

報告日期: 2007/10/16
報告時間: 16:00/16:50
報告學生: 林嬿琳
講評老師: 林以行

IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities

Nature Medicine 13, 927-34(2007)


Speaker: 林嬿琳 

Commentator: 林以行 老師

Time:2007/10/16 16:00-16:50

Place: Room 602



Sepsis, arose from severe bacterial infection and systemic inflammation, has been the clinical problem all over the world because of high mortality. It was evidenced that mast cells in the well-established animal model of sepsis, cecal ligation and puncture (CLP), protected mice from lethal effects. On the other hand, IL-15 plays an important role in innate immunity. Therefore, the author investigated whether IL-15 had the influence on mast cell-dependent antibacterial defenses in the course of sepsis. After CLP, mice deficient in IL-15 had much higher survival rate than those normally expressed IL-15. However, this detrimental effect of IL-15 seemed to be independent of IL-15Ra-mediated signals. Moreover, reconstitution of Il-15-/- mast cells in Kitw/Kitw-v mice rescued them from CLP, but not with wild-type mast cells. Based on these results, the author suggested sepsis survival and antibacterial immunity might be influenced by mast cell-derived intracellular IL-15. At basal levels, mast cells expressed intracellular IL-15. After LPS stimulation, intracellular IL-15 expression was increased and stored in granules, rather than secreted. Further, lack of IL-15 did not influence major distributions and functions of mast cells such as cytokine production, degranulation, and chemotaxis, except that the chymase activity of mast cells was up-regulated. The augmented chymase activity of mast cells in Il-15-/- mice enhanced the antibacterial ability and the production of neutrophil-infiltrating chemokines of mast cells. Besides, Mcpt2 (Mast cell protease 2) trancsription, one of the members of the chymase family, was directly down-modulated by intracellular IL-15. In conclusion, IL-15 could down-regulate mast cell-mediated innate immunity via controlling MCP2 expression.



1. Riedemann, N.C., Guo, R.F., Ward, P.A. Novel strategies for the treatment of sepsis.  Nat. Med. 9, 517-24 (2003).

2. Marshall, J.S. Mast-cell responses to pathogens. Nat. Rev. Immunol. 4, 787-99 (2004).