NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant

被引:171
作者
Besnard, A. -G. [2 ]
Guillou, N. [2 ]
Tschopp, J. [3 ]
Erard, F. [2 ]
Couillin, I. [2 ]
Iwakura, Y. [4 ]
Quesniaux, V. [2 ]
Ryffel, B. [1 ,2 ]
Togbe, D. [2 ,5 ]
机构
[1] Univ Orleans, UMR6218, F-45071 Orleans 2, France
[2] CNRS, F-45071 Orleans, France
[3] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland
[4] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Minato Ku, Tokyo, Japan
[5] Ctr Innovat, Artimmune SAS, Orleans, France
关键词
allergic inflammation; asthma; IL-1R1; NLRP3; inflammasome; DENDRITIC CELLS; NALP3; INFLAMMASOME; INTERLEUKIN-1; RECEPTOR; IMMUNE-RESPONSES; ALLERGIC-ASTHMA; MICE DEFICIENT; IL-1; CYTOKINES; ANTAGONIST; ACTIVATION;
D O I
10.1111/j.1398-9995.2011.02586.x
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
Background: Inflammasome activation with the production of IL-1 beta received substantial attention recently in inflammatory diseases. However, the role of inflammasome in the pathogenesis of asthma is not clear. Using an adjuvant-free model of allergic lung inflammation induced by ovalbumin (OVA), we investigated the role of NLRP3 inflammasome and related it to IL-1R1 signaling pathway. Methods: Allergic lung inflammation induced by OVA was evaluated in vivo in mice deficient in NLRP3 inflammasome, IL-1R1, IL-1 beta or IL-1 alpha. Eosinophil recruitment, Th2 cytokine, and chemokine levels were determined in bronchoalveolar lavage fluid, lung homogenates, and mediastinal lymph node cells ex vivo. Results: Allergic airway inflammation depends on NLRP3 inflammasome activation. Dendritic cell recruitment into lymph nodes, Th2 lymphocyte activation in the lung and secretion of Th2 cytokines and chemokines are reduced in the absence of NLRP3. Absence of NLRP3 and IL-1 beta is associated with reduced expression of other proinflammatory cytokines such as IL-5, IL-13, IL-33, and thymic stromal lymphopoietin. Furthermore, the critical role of IL-1R1 signaling in allergic inflammation is confirmed in IL-1R1-, IL-1 beta-, and IL-1 alpha-deficient mice. Conclusion: NLRP3 inflammasome activation leading to IL-1 production is critical for the induction of a Th2 inflammatory allergic response.
引用
收藏
页码:1047 / 1057
页数:11
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