title: Mannan binding lectin attenuates double-stranded RNA-mediated TLR3 activation and innate immunity.
abstract: 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.
authors: Department of Immunology, Southern Medical University, Guangzhou 510515, China.
authors: Hongzhi
authors: H
authors: Liu
authors: Department of Immunology, Southern Medical University, Guangzhou 510515, China.
authors: Jia
authors: J
authors: Zhou
authors: Department of Immunology, Southern Medical University, Guangzhou 510515, China.
authors: Di
authors: D
authors: Ma
authors: Department of Immunology, Southern Medical University, Guangzhou 510515, China.
authors: Xiao
authors: X
authors: Lu
authors: Department of Immunology, Southern Medical University, Guangzhou 510515, China.
authors: Siqi
authors: S
authors: Ming
authors: Department of Immunology, Southern Medical University, Guangzhou 510515, China; Guangzhou General Hospital of Guangzhou Military Command, Guangzhou 510010, China.
authors: Guiqiu
authors: G
authors: Shan
authors: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
authors: Xiaoyong
authors: X
authors: Zhang
authors: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China.
authors: Jinlin
authors: J
authors: Hou
authors: Department of Immunology, Southern Medical University, Guangzhou 510515, China. Electronic address: zhlchen@smu.edu.cn.
authors: Zhengliang
authors: Z
authors: Chen
authors: Department of Immunology, Southern Medical University, Guangzhou 510515, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310003, China. Electronic address: zdaming@smu.edu.cn.
authors: Daming
authors: D
authors: Zuo
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007369:Interferon Inducers / Q000494:pharmacology; D050835:Interferon Regulatory Factors / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D037601:Mannose-Binding Lectin / Q000502:physiology*; D010588:Phagosomes / Q000378:metabolism; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000502:physiology*; D017463:Receptors, Complement 3b / Q000378:metabolism; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000378:metabolism*
chemical_list: C509991:CR1 protein, human; D016207:Cytokines; D007369:Interferon Inducers; D050835:Interferon Regulatory Factors; D037601:Mannose-Binding Lectin; D012330:RNA, Double-Stranded; D017463:Receptors, Complement 3b; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; D011070:Poly I-C
keywords: Dendritic cell; Double-stranded RNA; Mannan binding lectin; Monocyte; Toll like receptor 3