Immune inhibitory receptors: essential regulators of phagocyte function

Abstract

Phagocytes, including neutrophils, monocytes, and macrophages, play a crucial role in host defense by recognition and elimination of invading pathogens. Phagocytic cells produce reactive oxygen species (ROS), inflammatory cytokines, and chemokines, leading to bacterial killing and to recruitment and activation of additional immune cells. However, inflammatory mediators are potentially harmful for the host and their production is therefore tightly controlled by multiple regulatory mechanisms. One such mechanism is immune suppression by immune inhibitory receptors, which are increasingly acknowledged as potent regulators of the immune response. So far, research has focused on the role of these receptors in the regulation of NK cells, B cells, and T cells. Importantly, an accumulating number of inhibitory receptors have been identified on phagocytes. Here, we review the role of inhibitory receptors in the regulation of phagocyte cytokine production, migration, apoptosis, ROS production, and phagocytosis. Furthermore, we discuss the intracellular mechanisms utilized by distinct inhibitory receptors to regulate specific phagocyte functions. We demonstrate that inhibitory receptors are important regulators of the immune response, which bacteria can use to their advantage.