Rethinking Communication in the Immune System: The Quorum Sensing Concept

Abstract

Quorum sensing was first described as the communication process bacteria employ to coordinate changes in gene expression and therefore, their collective behavior in response to population density. Emerging new evidence suggests that quorum sensing can also contribute to the regulation of immune cell responses. Quorum sensing might be achieved by the ability of immune cells to perceive the density of their own populations or those of other cells in their environment; responses to alterations in cell density might then be coordinated via changes in gene expression and protein signaling. Quorum sensing mechanisms can regulate T and B cell as well as macrophage function. We posit that perturbations in quorum sensing may undermine the balance between diverse immune cell populations and predispose the host to immune abnormalities.

Figure 1.. Bacterial quorum sensing.

Bacteria use signaling molecules (inducers) that are released into the environment, to communicate with each other. The term ‘quorum sensing’ (QS) describes the phenomenon through which signaling molecules enable a single cell to sense the number of bacteria in its environment (cell density) and to adjust their behavior, helping to shape and maintain the behavior of the entire bacterial population.

Figure 2.. IL-2 as a critical player in immune quorum sensing.

IL-2-producing T cells are “master regulators” of CD4⁺CD25⁺ T_Reg cells, as they are essential for the maintenance of IL-2-dependent T_Reg populations. Quorum-sensing is mediated by a negative feedback loop between T_Regs and IL-2-producing T cells, as T_Regs curb the number of IL-2-producing T cells. IL-2 is the quorum sensing autoinducer in this system.

Figure 3.. Quorum sensing of tissue-resident macrophages in homeostasis.

Competition for CSF1 controls the population density, as low CSF1 signaling is required for macrophage survival, while high CSF1 signaling drives macrophage proliferation. Higher concentrations of circulating CSF1 also drive myelopoiesis in the bone-marrow. Macrophage activation states can spread within the macrophage network through paracrine signaling of activating and de-activating cytokines such as TNF/IL-1β and IL-10, respectively. At inflammatory sites, nitric oxide (NO) can reduce mitochondrial respiration and cellular ATP:ADP ratios. The density of NO-producing cells can control immune cell activity at the tissue level; thus, NO production can act as a quorum sensing mechanism to help terminate inflammation.