https://scholars.lib.ntu.edu.tw/handle/123456789/414229
標題: | Dectin-2 is a primary receptor for NLRP3 inflammasome activation in dendritic cell response to Histoplasma capsulatum | 作者: | Chang, Tzu-Hsuan Huang, Juin-Hua Lin, Hsiu-Chao Chen, Wen-Yu Lee, Yu-Hsiang LI-CHUNG HSU Netea, Mihai G Ting, Jenny P-Y BETTY AN-YE WU-HSIEH |
公開日期: | 七月-2017 | 出版社: | PUBLIC LIBRARY SCIENCE | 卷: | 13 | 期: | 7 | 來源出版物: | PLoS pathogens | 摘要: | Inflammasome is an intracellular protein complex that serves as cytosolic pattern recognition receptor (PRR) to engage with pathogens and to process cytokines of the interleukin-1 (IL-1) family into bioactive molecules. It has been established that interleukin-1β (IL-1β) is important to host defense against Histoplasma capsulatum infection. However, the detailed mechanism of how H. capsulatum induces inflammasome activation leading to IL-1β production has not been studied. Here, we showed in dendritic cells (DCs) that H. capsulatum triggers caspase-1 activation and IL-1β production through NLRP3 inflammasome. By reciprocal blocking of Dectin-1 or Dectin-2 in single receptor-deficient DCs and cells from Clec4n-/-, Clec7a-/-, and Clec7a-/-Clec4n-/- mice, we discovered that while Dectin-2 operates as a primary receptor, Dectin-1 serves as a secondary one for NLRP3 inflammasome. In addition, both receptors trigger Syk-JNK signal pathway to activate signal 1 (pro-IL-1β synthesis) and signal 2 (activation of caspase-1). Results of pulmonary infection with H. capsulatum showed that CD103+ DCs are one of the major producers of IL-1β and Dectin-2 and Dectin-1 double deficiency abolishes their IL-1β response to the fungus. While K+ efflux and cathepsin B (but not ROS) function as signal 2, viable but not heat-killed H. capsulatum triggers profound lysosomal rupture leading to cathepsin B release. Interestingly, cathepsin B release is regulated by ERK/JNK downstream of Dectin-2 and Dectin-1. Our study demonstrates for the first time the unique roles of Dectin-2 and Dectin-1 in triggering Syk-JNK to activate signal 1 and 2 for H. capsulatum-induced NLRP3 inflammasome activation. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85026775424&doi=10.1371%2fjournal.ppat.1006485&partnerID=40&md5=12a103ef27de4ce4666c45d9d48d71c0 https://scholars.lib.ntu.edu.tw/handle/123456789/414229 |
ISSN: | 1553-7366 | DOI: | 10.1371/journal.ppat.1006485 |
顯示於: | 免疫學研究所 |
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