Signalling through MyD88 drives surface expression of the mycobacterial receptors MCL (Clecsf8, Clec4d) and Mincle (Clec4e) following microbial stimulation

Microbes Infect. 2016 Jul-Aug;18(7-8):505-9. doi: 10.1016/j.micinf.2016.03.007. Epub 2016 Mar 19.

Abstract

The heterodimeric mycobacterial receptors, macrophage C-type lectin (MCL) and macrophage inducible C-type lectin (Mincle), are upregulated at the cell surface following microbial challenge, but the mechanisms underlying this response are unclear. Here we report that microbial stimulation triggers Mincle expression through the myeloid differentiation primary response gene 88 (MyD88) pathway; a process that does not require MCL. Conversely, we show that MCL is constitutively expressed but retained intracellularly until Mincle is induced, whereupon the receptors form heterodimers which are translocated to the cell surface. Thus this "two-step" model for induction of these key receptors provides new insights into the underlying mechanisms of anti-mycobacterial immunity.

Keywords: C-type lectin receptor; Clec4d; Clec4e; Dectin-3; MyD88; TLR signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Gene Expression
  • Host-Pathogen Interactions*
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Macrophages / immunology
  • Macrophages / microbiology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice, Inbred C57BL
  • Mycobacterium / immunology*
  • Myeloid Differentiation Factor 88 / metabolism*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*

Substances

  • Clec4d protein, mouse
  • Clecsf8 protein, mouse
  • Lectins, C-Type
  • Membrane Proteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Cell Surface
  • Receptors, Immunologic