Adenosine-5'-Triphosphate (ATP) Protects Mice against Bacterial Infection by Activation of the NLRP3 Inflammasome

It has been established that Adenosine-5'-triphosphate (ATP) can activate the NLRP3 inflammasome. However, the physiological effect of extracellular ATP on NLRP3 inflammasome activation has not yet been investigated. In the present study, we found that ATP was indeed released during bacterial infection. By using a murine peritonitis model, we also found that ATP promotes the fight against bacterial infection in mice. ATP induced the secretion of IL-1 beta and chemokines by murine bone marrow-derived macrophages in vitro. Furthermore, the intraperitoneal injection of ATP elevated the levels of IL-1b and chemokines in the mouse peritoneal lavage. Neutrophils were rapidly recruited to the peritoneum after ATP injection. In addition, the effects on cytokine and chemokine secretion and neutrophil recruitment were markedly attenuated by the pre-administration of the caspase-1 inhibitor Ac-YVAD-cho. Ac-YVAD-cho also significantly attenuated the protective effect of ATP against bacterial infection. In the present study, we demonstrated a protective role for ATP during bacterial infection and this effect was related to NLRP3 inflammasome activation. Together, these results suggest a role for ATP in initiating the immune response in hosts suffering from infections.