A Metabolism-Based Quorum Sensing Mechanism Contributes to Termination of Inflammatory Responses

Recruitment of immune cells with antimicrobial activities is essential to fight local infections but has the potential to trigger immunopathology. Whether the immune system has the ability to sense inflammation intensity and self-adjust accordingly to limit tissue damage remains to be fully established. During local infection with an intracellular pathogen, we have shown that nitric oxide (NO) produced by recruited monocyte-derived cells was essential to limit inflammation and cell recruitment. Mechanistically, we have provided evidence that NO dampened monocyte-derived cell cytokine and chemokine production by inhibiting cellular respiration and reducing cellular ATP:ADP ratio. Such metabolic control operated at the tissue level but only when a sufficient number of NO-producing cells reached the site of infection. Thus, NO production and activity act as a quorum sensing mechanism to help terminate the inflammatory response. [Display omitted] •NO limits cytokine production by monocyte-derived cells during L. major infection•NO reduces mitochondrial respiration and cellular ATP:ADP ratio in vivo•The density of NO-producing cells controls immune cell activity at the tissue level•NO production acts as a quorum sensing mechanism to help terminate inflammation Mechanisms sensing when a sufficient number of immune cells have accumulated in tissues to terminate inflammation are incompletely understood. Here, Postat et al. establish that NO produced at inflammatory sites acts as a quorum sensing mechanism to adjust monocyte-derived cell respiration and cytokine production to their density in the tissue.