Quorum Sensing by Monocyte-Derived Populations

Abstract

Quorum sensing is a type of cellular communication that was first described in bacteria, consisting of gene expression regulation in response to changes in cell-population density. Bacteria synthesize and secrete diffusive molecules called autoinducers, which concentration varies accordingly with cell density and can be detected by the producing cells themselves. Once autoinducer concentration reaches a critical threshold, all bacteria within the autoinducer-rich environment react by modifying their genetic expression and adopt a coordinated behavior (e.g., biofilm formation, virulence factor expression, or swarming motility). Recent advances highlight the possibility that such type of communication is not restricted to bacteria, but can exist among other cell types, including immune cells and more specifically monocyte-derived cells (1). For such cells, quorum sensing mechanisms may not only regulate their population size and synchronize their behavior at homeostasis but also alter their activity and function in unexpected ways during immune reactions. Although the nature of immune autoinducers and cellular mechanisms remains to be fully characterized, quorum sensing mechanisms in the immune system challenge our traditional conception of immune cell interactions and likely represent an important mode of communication at homeostasis or during an immune response. In this mini-review, we briefly present the prototypic features of quorum sensing in bacteria and discuss the existing evidence for quorum sensing within the immune system. Mainly, we review quorum sensing mechanisms among monocyte-derived cells, such as the regulation of inflammation by the density of monocyte-derived cells that produce nitric oxide and discuss the relevance of such models in the context of immune-related pathologies.

Keywords: macrophage; metabolism; monocyte; monocyte-derived cell; nitric oxide; quorum sensing (QS).

Figure 1

Quorum sensing in bacteria. To communicate and synchronize their behavior, bacteria (green rectangles) use quorum sensing. Each bacterium produces a low quantity of a membrane-diffusive molecule called autoinducer (blue triangles), which biological activity is absent at low concentration. Bacterial growth over time increases cell density together with the concentration of the autoinducer in the extracellular environment. Once a sufficient number of bacteria have accumulated, hence reaching a sufficient density, the autoinducer concentration is high enough to initiate biological alterations. In bacteria, the autoinducer often triggers a switch in genetic expression, after binding to transcriptional regulators. Such a genetic switch leads to the emergence of group behaviors such as biofilm formation, increased pathogenicity, or swarming motility.

Figure 2

Quorum sensing among mononuclear phagocytes at the site of infection by intracellular pathogens. Mononuclear phagocytes are endowed with a quorum sensing mechanism during the immune reaction against Leishmania major parasites. Local skin infection with this intracellular pathogen elicits inflammation and the recruitment of innate immune cells from the blood, including monocytes (small round green cells) that differentiate into mononuclear phagocytes (large rough green cells) at the site of the immune reaction. Such cells sustain monocyte infiltration and differentiation by secreting cytokine and chemokine (yellow circles) but also produce nitric oxide (blue triangles, NO) that diffuses within the microenvironment and helps fight the infection. Such mechanism increases mononuclear phagocyte number at the site of infection during the early phases of the response, allowing for local control of the pathogen load. Once a sufficient number of mononuclear phagocytes have accumulated, NO starts to repress cellular respiration (red cross on the mitochondria), dampening the cellular ATP:ADP ratio and ultimately limiting cytokine and chemokine secretion that is needed for immune cell recruitment. The mechanism relies on NO that diffuses and acts on every mononuclear phagocyte, independently of their iNOS expression, and only exists when a sufficient number of cells have accumulated. Therefore, NO acts as an autoinducer for mononuclear phagocytes, limiting their recruitment and the development of an immunopathology but only when a sufficient number of cells have accumulated to control the infection efficiently.