Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration

Nat Commun. 2014 Aug 19;5:4710. doi: 10.1038/ncomms5710.

Abstract

Inflammatory monocytes play an important role in host defense against infections. However, the regulatory mechanisms of transmigration into infected tissue are not yet completely understood. Here we show that mice deficient in MAIR-II (also called CLM-4 or LMIR2) are more susceptible to caecal ligation and puncture (CLP)-induced peritonitis than wild-type (WT) mice. Adoptive transfer of inflammatory monocytes from WT mice, but not from MAIR-II, TLR4 or MyD88-deficient mice, significantly improves survival of MAIR-II-deficient mice after CLP. Migration of inflammatory monocytes into the peritoneal cavity after CLP, which is dependent on VLA-4, is impaired in above mutant and FcRγ chain-deficient mice. Lipopolysaccharide stimulation induces association of MAIR-II with FcRγ chain and Syk, leading to enhancement of VLA-4-mediated adhesion to VCAM-1. These results indicate that activation of MAIR-II/FcRγ chain by TLR4/MyD88-mediated signalling is essential for the transmigration of inflammatory monocytes from the blood to sites of infection mediated by VLA-4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cecum
  • Cell Adhesion / physiology
  • Cell Movement / physiology*
  • Disease Models, Animal
  • Female
  • Inflammation / etiology
  • Inflammation / pathology*
  • Inflammation / physiopathology
  • Integrin alpha4beta1 / physiology*
  • Ligation
  • Lipopolysaccharides / adverse effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / pathology*
  • Monocytes / physiology
  • Myeloid Differentiation Factor 88 / deficiency
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / physiology
  • Peritonitis / etiology
  • Peritonitis / pathology
  • Peritonitis / physiopathology
  • Receptors, Immunologic / deficiency
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*
  • Receptors, Polymeric Immunoglobulin / deficiency
  • Receptors, Polymeric Immunoglobulin / genetics
  • Receptors, Polymeric Immunoglobulin / physiology*
  • Signal Transduction / physiology
  • Toll-Like Receptor 4 / deficiency
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / physiology*

Substances

  • Integrin alpha4beta1
  • LMIR2 protein, mouse
  • Lipopolysaccharides
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Immunologic
  • Receptors, Polymeric Immunoglobulin
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • myeloid-associated Ig-like receptor , mouse