title: 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.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
authors.forename: Qian
authors.initials: Q
authors.lastname: Gao
authors.forename: Sheng-An
authors.initials: SA
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Zhou
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Guo
authors.forename: Wenhui
authors.initials: W
authors.lastname: Lee
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D020170:Caspase 1 / Q000276:immunology / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000276:immunology / Q000378:metabolism; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010538:Peritonitis / Q000276:immunology / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D000255:Adenosine Triphosphate; D020170:Caspase 1