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Mannan binding lectin attenuates double‐stranded RNA‐mediated TLR3 activation and innate immunity
Author(s) -
Liu Hongzhi,
Zhou Jia,
Ma Di,
Lu Xiao,
Ming Siqi,
Shan Guiqiu,
Zhang Xiaoyong,
Hou Jinlin,
Chen Zhengliang,
Zuo Daming
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.01.064
Subject(s) - tlr3 , mannan binding lectin , innate immune system , collectin , microbiology and biotechnology , pattern recognition receptor , complement system , ficolin , lectin , chemistry , receptor , biology , toll like receptor , immune system , biochemistry , immunology
Mannan binding lectin (MBL) functions as a pattern recognition molecule (PRM) which is able to initiate complement activation. Here, we characterize a previously unrecognized attribute of MBL as a double‐stranded RNA (dsRNA) binding protein capable of modifying Toll like receptor 3 (TLR3) activation. MBL interacts with poly(I:C) and suppresses poly(I:C)‐induced activation of TLR3 pathways and subsequent cytokine production. In addition, MBL binds to TLR3 directly. Surprisingly, disrupting the interaction between MBL and complement receptor 1 (CR1) or restraining the traffic of MBL to phagosome reversed the MBL limited TLR3 activation. We demonstrate the importance of MBL guided ligands intracellular localization, emphasizing the significance of understanding the dynamics of TLR agonists complexed with MBL or other PRMs inside the cell in immune defense.