C-type lectin receptors Dectin-3 and Dectin-2 form a heterodimeric pattern-recognition receptor for host defense against fungal infection

Immunity. 2013 Aug 22;39(2):324-34. doi: 10.1016/j.immuni.2013.05.017. Epub 2013 Aug 1.

Abstract

C-type lectin receptors (CLRs) play critical roles as pattern-recognition receptors (PRRs) for sensing Candida albicans infection, which can be life-threatening for immunocompromised individuals. Here we have shown that Dectin-3 (also called CLECSF8, MCL, or Clec4d), a previously uncharacterized CLR, recognized α-mannans on the surfaces of C. albicans hyphae and induced NF-κB activation. Mice with either blockade or genetically deleted Dectin-3 were highly susceptible to C. albicans infection. Dectin-3 constantly formed heterodimers with Dectin-2, a well-characterized CLR, for recognizing C. albicans hyphae. Compared to their respective homodimers, Dectin-3 and Dectin-2 heterodimers bound α-mannans more effectively, leading to potent inflammatory responses against fungal infections. Together, our study demonstrates that Dectin-3 forms a heterodimeric PRR with Dectin-2 for sensing fungal infection and suggests that different CLRs may form different hetero- and homodimers, which provide different sensitivity and diversity for host cells to detect various microbial infections.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida albicans / immunology*
  • Candidiasis / immunology*
  • Enzyme Activation
  • Female
  • Humans
  • Hyphae / immunology
  • Hyphae / metabolism
  • Lectins, C-Type / deficiency
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Mannans / metabolism
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NF-kappa B / metabolism
  • Receptors, Pattern Recognition / immunology
  • Signal Transduction

Substances

  • Clecsf8 protein, mouse
  • Lectins, C-Type
  • Mannans
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Pattern Recognition
  • dectin-2, mouse