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Sci Signal ; 5(210): ra12, 2012 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-22317922

RESUMO

Macrophage ingestion of the yeast Candida albicans requires its recognition by multiple receptors and the activation of diverse signaling programs. Synthesis of the lipid mediator prostaglandin E(2) (PGE(2)) and generation of cyclic adenosine monophosphate (cAMP) also accompany this process. Here, we characterized the mechanisms underlying PGE(2)-mediated inhibition of phagocytosis and filamentous actin (F-actin) polymerization in response to ingestion of C. albicans by alveolar macrophages. PGE(2) suppressed phagocytosis and F-actin formation through the PGE(2) receptors EP2 and EP4, cAMP, and activation of types I and II protein kinase A. Dephosphorylation and activation of the actin depolymerizing factor cofilin-1 were necessary for these inhibitory effects of PGE(2). PGE(2)-dependent activation of cofilin-1 was mediated by the protein phosphatase activity of PTEN (phosphatase and tensin homolog deleted on chromosome 10), with which it directly associated. Because enhanced production of PGE(2) accompanies many immunosuppressed states, the PTEN-dependent pathway described here may contribute to impaired antifungal defenses.


Assuntos
Candida albicans/imunologia , Candidíase/imunologia , Cofilina 1/imunologia , Dinoprostona/imunologia , Tolerância Imunológica , Macrófagos Alveolares/imunologia , PTEN Fosfo-Hidrolase/imunologia , Fagocitose/imunologia , Actinas/imunologia , Actinas/metabolismo , Animais , Candida albicans/metabolismo , Candidíase/metabolismo , Células Cultivadas , Cofilina 1/metabolismo , AMP Cíclico/imunologia , AMP Cíclico/metabolismo , Proteína Quinase Tipo I Dependente de AMP Cíclico/imunologia , Proteína Quinase Tipo I Dependente de AMP Cíclico/metabolismo , Proteína Quinase Tipo II Dependente de AMP Cíclico/imunologia , Proteína Quinase Tipo II Dependente de AMP Cíclico/metabolismo , Dinoprostona/biossíntese , Feminino , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/microbiologia , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação/imunologia , Ratos , Ratos Wistar , Receptores de Prostaglandina E Subtipo EP2/imunologia , Receptores de Prostaglandina E Subtipo EP2/metabolismo , Receptores de Prostaglandina E Subtipo EP4/imunologia , Receptores de Prostaglandina E Subtipo EP4/metabolismo
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