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Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection.

Salina AC, Souza TP, Serezani CH, Medeiros AI
Innate Immun. 2017 23 (3): 219-227

PMID: 28359217 · DOI:10.1177/1753425916684934

Alveolar macrophages (AMs) are multitasking cells that maintain lung homeostasis by clearing apoptotic cells (efferocytosis) and performing antimicrobial effector functions. Different PRRs have been described to be involved in the binding and capture of non-opsonized Streptococcus pneumoniae, such as TLR-2, mannose receptor (MR) and scavenger receptors (SRs). However, the mechanism by which the ingestion of apoptotic cells negatively influences the clearance of non-opsonized S. pneumoniae remains to be determined. In this study, we evaluated whether the prostaglandin E2 (PGE) produced during efferocytosis by AMs inhibits the ingestion and killing of non-opsonized S. pneumoniae. Resident AMs were pre-treated with an E prostanoid (EP) receptor antagonist, inhibitors of cyclooxygenase and protein kinase A (PKA), incubated with apoptotic Jurkat T cells, and then challenged with S. pneumoniae. Efferocytosis slightly decreased the phagocytosis of S. pneumoniae but greatly inhibited bacterial killing by AMs in a manner dependent on PGE production, activation of the EP2-EP4/cAMP/PKA pathway and inhibition of HO production. Our data suggest that the PGE produced by AMs during efferocytosis inhibits HO production and impairs the efficient clearance non-opsonized S. pneumoniae by EP2-EP4/cAMP/PKA pathway.

MeSH Terms (20)

Animals Apoptosis Bacteriolysis Cyclic AMP Cyclic AMP-Dependent Protein Kinases Dinoprostone Female Homeostasis Humans Hydrogen Peroxide Jurkat Cells Macrophages, Alveolar Phagocytosis Pneumococcal Infections Rats Rats, Wistar Receptors, Prostaglandin E, EP2 Subtype Receptors, Prostaglandin E, EP4 Subtype Signal Transduction Streptococcus pneumoniae

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