Mannan binding lectin attenuates double-stranded RNA-mediated TLR3 activation and innate immunity

FEBS Lett. 2014 Mar 18;588(6):866-72. doi: 10.1016/j.febslet.2014.01.064. Epub 2014 Feb 11.

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.

Keywords: Dendritic cell; Double-stranded RNA; Mannan binding lectin; Monocyte; Toll like receptor 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytokines / metabolism
  • Humans
  • Immunity, Innate*
  • Interferon Inducers / pharmacology
  • Interferon Regulatory Factors / metabolism
  • Leukocytes, Mononuclear / immunology*
  • Mannose-Binding Lectin / physiology*
  • Phagosomes / metabolism
  • Poly I-C / pharmacology
  • RNA, Double-Stranded / physiology*
  • Receptors, Complement 3b / metabolism
  • Signal Transduction
  • Toll-Like Receptor 3 / metabolism*

Substances

  • CR1 protein, human
  • Cytokines
  • Interferon Inducers
  • Interferon Regulatory Factors
  • Mannose-Binding Lectin
  • RNA, Double-Stranded
  • Receptors, Complement 3b
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Poly I-C