Signalling lymphocyte activation molecule family member 9 is found on select subsets of antigen-presenting cells and promotes resistance to Salmonella infection

Immunology. 2020 Apr;159(4):393-403. doi: 10.1111/imm.13169. Epub 2020 Jan 28.

Abstract

Signalling lymphocyte activation molecule family member 9 (SLAMF9) is an orphan receptor of the CD2/SLAM family of leucocyte surface proteins. Examination of SLAMF9 expression and function indicates that SLAMF9 promotes inflammation by specialized subsets of antigen-presenting cells. Within healthy liver and circulating mouse peripheral blood mononuclear cells, SLAMF9 is expressed on CD11b+ , Ly6C- , CD11clow , F4/80low , MHC-II+ , CX3 CR1+ mononuclear phagocytes as well as plasmacytoid dendritic cells. In addition, SLAMF9 can be found on peritoneal B1 cells and small (F4/80low ), but not large (F4/80high ), peritoneal macrophages. Upon systemic challenge with Salmonella enterica Typhimurium, Slamf9-/- mice were impaired in their ability to clear the infection from the liver. In humans, SLAMF9 is up-regulated upon differentiation of monocytes into macrophages, and lipopolysaccharide stimulation of PMA-differentiated, SLAMF9 knockdown THP-1 cells showed an essential role of SLAMF9 in production of granulocyte-macrophage colony-stimulating factor, tumour necrosis factor-α, and interleukin-1β. Taken together, these data implicate SLAMF9 in the initiation of inflammation and clearance of bacterial infection.

Keywords: Salmonella; SLAMF9; dendritic cells; inflammation; mononuclear phagocytes.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology
  • B-Lymphocytes / microbiology
  • Cell Differentiation
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Dendritic Cells / microbiology
  • Gene Expression Regulation
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / immunology
  • Lipopolysaccharides / pharmacology
  • Liver / immunology*
  • Liver / microbiology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / drug effects
  • Monocytes / immunology
  • Monocytes / microbiology
  • Salmonella Infections / genetics
  • Salmonella Infections / immunology*
  • Salmonella Infections / microbiology
  • Salmonella typhimurium / immunology*
  • Salmonella typhimurium / pathogenicity
  • Signal Transduction
  • Signaling Lymphocytic Activation Molecule Family / deficiency
  • Signaling Lymphocytic Activation Molecule Family / genetics
  • Signaling Lymphocytic Activation Molecule Family / immunology*
  • THP-1 Cells
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • IL1B protein, human
  • Interleukin-1beta
  • Lipopolysaccharides
  • SLAMF9 protein, human
  • Signaling Lymphocytic Activation Molecule Family
  • Slamf9 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Granulocyte-Macrophage Colony-Stimulating Factor