Mice Lacking the Purinergic Receptor P2X5 Exhibit Defective Inflammasome Activation and Early Susceptibility to Listeria monocytogenes.

P2X5 is a member of the P2X purinergic receptor family of ligand-gated cation channels and has recently been shown to regulate inflammatory bone loss. In this study, we report that P2X5 is a protective immune regulator during Listeria monocytogenes infection, as P2X5-deficient mice exhibit increased bacterial loads in the spleen and liver, increased tissue damage, and early (within 3-6 d) susceptibility to systemic L. monocytogenes infection. Whereas P2X5-deficient mice experience normal monocyte recruitment in response to L. monocytogenes, P2X5-deficient bone marrow-derived macrophages (BMMs) exhibit defective cytosolic killing of L. monocytogenes We further showed that P2X5 is required for L. monocytogenes-induced inflammasome activation and IL-1β production and that defective L. monocytogenes killing in P2X5-deficient BMMs is substantially rescued by exogenous IL-1β or IL-18. Finally, in vitro BMM killing and in vivo L. monocytogenes infection experiments employing either P2X7 deficiency or extracellular ATP depletion suggest that P2X5-dependent anti-L. monocytogenes immunity is independent of the ATP-P2X7 inflammasome activation pathway. Together, our findings elucidate a novel and specific role for P2X5 as a critical mediator of protective immunity. Copyright © 2020 by The American Association of Immunologists, Inc.

Citation

Yun Hee Jeong, Matthew C Walsh, Jiyeon Yu, Hao Shen, E John Wherry, Yongwon Choi. Mice Lacking the Purinergic Receptor P2X5 Exhibit Defective Inflammasome Activation and Early Susceptibility to Listeria monocytogenes. Journal of immunology (Baltimore, Md. : 1950). 2020 Aug 01;205(3):760-766

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PMID: 32540996

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