Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Induction of B7-H6, a ligand for the Natural Killer cell activating receptor NKp30, in inflammatory conditions

Abstract

B7-H6, a member of the B7 family of immunoreceptors, is as a cell surface ligand for the NKp30 activating receptor expressed on Natural Killer (NK) cells. B7-H6 is not detected in normal human tissues at steady-state but is expressed on tumor cells. However, whether B7-H6 can be expressed in other conditions remains unknown. We analyzed here the pathways that lead to the expression of B7-H6 in non-transformed cells. In vitro, B7-H6 was induced at the surface of CD14+CD16+ pro-inflammatory monocytes and neutrophils upon stimulation by ligands of Toll-like receptors or pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα). In these conditions, a soluble form of B7-H6 (sB7-H6) was also produced by activated monocytes and neutrophils. In vivo, B7-H6 was expressed on circulating pro-inflammatory CD14+CD16+ monocytes in a group of patients in sepsis conditions, and was linked to an increased mortality. sB7-H6 was selectively detected in the sera of patients with Gram- sepsis and was associated with membrane vesicles that co-sedimented with the exosomal fraction. These findings reveal that B7-H6 is not only implicated in tumor immunosurveillance but also participates to the inflammatory response in infectious conditions.