Signalling Lymphocyte Activation Molecule Family Member 9 Is Found On Select Subsets Of Antigen-Presenting Cells And Promotes Resistance To Salmonella Infection

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(-), CD11c(low), F4/80(low), MHC-II+, CX(3)CR1(+) mononuclear phagocytes as well as plasmacytoid dendritic cells. In addition, SLAMF9 can be found on peritoneal B1 cells and small (F4/80(low)), but not large (F4/80(high)), 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-alpha, and interleukin-1 beta. Taken together, these data implicate SLAMF9 in the initiation of inflammation and clearance of bacterial infection.