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
附件下載:

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

 

Abstract:

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.

 

References:

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).