Mice Lacking the Purinergic Receptor P2X5 Exhibit Defective Inflammasome Activation and Early Susceptibility to Listeria monocytogenes.
J Immunol
; 205(3): 760-766, 2020 08 01.
Article
en En
| MEDLINE
| ID: mdl-32540996
ABSTRACT
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-1ß production and that defective L. monocytogenes killing in P2X5-deficient BMMs is substantially rescued by exogenous IL-1ß 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.
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1
Banco de datos:
MEDLINE
Asunto principal:
Monocitos
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Inflamasomas
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Receptores Purinérgicos P2X5
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Listeriosis
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Listeria monocytogenes
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Macrófagos
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2020
Tipo del documento:
Article