Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection.
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 (PGE2) 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 PGE2 production, activation of the EP2-EP4/cAMP/PKA pathway and inhibition of H2O2 production. Our data suggest that the PGE2 produced by AMs during efferocytosis inhibits H2O2 production and impairs the efficient clearance non-opsonized S. pneumoniae by EP2-EP4/cAMP/PKA pathway.
['Salina|Ana Cg|AC|', 'Souza|Tais P|TP|', 'Serezani|Carlos H|CH|', 'Medeiros|Alexandra I|AI|']
D000818:Animals D017209:Apoptosis D001433:Bacteriolysis D000242:Cyclic AMP D017868:Cyclic AMP-Dependent Protein Kinases D015232:Dinoprostone D005260:Female D006706:Homeostasis D006801:Humans D006861:Hydrogen Peroxide D019169:Jurkat Cells D016676:Macrophages, Alveolar D010587:Phagocytosis D011008:Pneumococcal Infections D051381:Rats D017208:Rats, Wistar D058307:Receptors, Prostaglandin E, EP2 Subtype D058309:Receptors, Prostaglandin E, EP4 Subtype D015398:Signal Transduction D013296:Streptococcus pneumoniae
prostaglandin E2 alveolar macrophages Streptococcus pneumoniae apoptotic cells Efferocytosis