IrFC - An Ixodes ricinus injury-responsive molecule related to Limulus Factor C

Dev Comp Immunol. 2014 Oct;46(2):439-47. doi: 10.1016/j.dci.2014.05.016. Epub 2014 Jun 9.


Limulus Clotting Factor C is a multi-domain serine protease that triggers horseshoe crab hemolymph clotting in the presence of trace amounts of bacterial lipopolysaccharides. Here we describe and functionally characterize an homologous molecule, designated as IrFC, from the hard tick Ixodes ricinus. Tick Factor C consists of an N-terminal cysteine-rich domain, four complement control protein (sushi) modules, an LCCL domain, a truncated C-lectin domain and a C-terminal trypsin-type domain. Developmental expression profiling by quantitative real-time PCR revealed that the irfc mRNA is expressed in all stages including eggs. In tissues dissected from adult I. ricinus females, the irfc mRNA is present mainly in tick hemocytes and accordingly, indirect immunofluorescence microscopy localized IrFC intracellularly, in tick hemocytes. Irfc mRNA levels were markedly increased upon injection of sterile saline, or different microbes, demonstrating that the irfc gene transcription occurs in response to injury. This indicates a possible role of IrFC in hemolymph clotting and/or wound healing, although these defense mechanisms have not been yet definitely demonstrated in ticks. RNAi silencing of irfc expression resulted in a significant reduction in phagocytic activity of tick hemocytes against the Gram-negative bacteria Chryseobacterium indologenes and Escherichia coli, but not against the yeast, Candida albicans. This result suggests that IrFC plays a role in the tick primordial complement system and as such possibly mediates transmission of tick-borne pathogens.

Keywords: Complement; Innate immunity; Limulus Clotting Factor C; Phagocytosis; RNA interference; Tick Ixodes ricinus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthropod Proteins / biosynthesis
  • Arthropod Proteins / genetics*
  • Borrelia / immunology
  • Candida albicans / immunology
  • Complement System Proteins / physiology
  • Enzyme Precursors / biosynthesis
  • Enzyme Precursors / genetics*
  • Escherichia coli / immunology
  • Female
  • Gene Expression
  • Immunity, Innate
  • Ixodes / enzymology
  • Ixodes / genetics*
  • Ixodes / immunology
  • Ixodes / microbiology
  • Male
  • Micrococcus luteus / immunology
  • Molecular Sequence Data
  • Phagocytosis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Serine Endopeptidases / biosynthesis
  • Serine Endopeptidases / genetics*
  • Up-Regulation / immunology


  • Arthropod Proteins
  • Enzyme Precursors
  • RNA, Messenger
  • Complement System Proteins
  • Serine Endopeptidases
  • Limulus clotting factor C

Associated data

  • GENBANK/KJ150729