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

Abstract

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-1β and chemokines by murine bone marrow-derived macrophages in vitro. Furthermore, the intraperitoneal injection of ATP elevated the levels of IL-1β 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.

Consensus guidelines for the detection of immunogenic cell death

“…141,[177][178][179] Moreover, extracellular ATP promotes the activation of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome in APCs, hence stimulating the processing and release of interleukin (IL)-1b and IL-18. 119,[180][181][182][183][184][185][186][187][188][189] In line with this notion, the immunogenic potential of cells succumbing to ICD can be significantly reduced by pharmacological or genetic interventions that limit the availability of ATP in the pericellular space, such as the administration of recombinant apyrase (an ATP-degrading enzyme) or the transfection-enforced overexpression of ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1, best known as CD39), which converts ATP into ADP and AMP. 190 Intriguingly, CD39 and 5 0 -nucleotidase, ecto (NT5E, best known as CD73), which transforms AMP into adenosine, are often overexpressed by malignant tissues.…”

P2X ion channel receptors and inflammation

“…ATP activation of the NLRP3 inflammasome protects mice against bacterial infection [122]. The P2X7 receptor plays a role in acute and chronic stages of infection as well as a 'danger signal' in the initial stages of inflammation (see [71]).…”

Toll-Like Receptor-Triggered Calcium Mobilization Protects Mice against Bacterial Infection through Extracellular ATP Release

“…Recently, the physiological effect of extracellular ATP on NLRP3 inflammasome activation was investigated in the context of bacterial infection (16). Why and how ATP is released during bacterial infection are still unknown.…”

“…The mechanisms of ATP release are well characterized for vesicular cells and excitatory/ secretory tissues; however, the mechanisms of ATP release from immune cells, such as macrophages, have not been well characterized. Actually, a recent paper showed that ATP could be released from infected immune cells and immune responses upregulated through activating NLRP3 inflammasomes, but the correlation between ATP release and Toll-like receptor (TLR) signaling is still indistinct (16). Therefore, the exploration of the internal relationship between ATP release and TLR-mediated innate immune responses against bacterial infection is justified and worthwhile.…”