title: Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection.
abstract: 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 PGE2production, activation of the EP2-EP4/cAMP/PKA pathway and inhibition of H2O2production. Our data suggest that the PGE2produced by AMs during efferocytosis inhibits H2O2production and impairs the efficient clearance non-opsonized S. pneumoniae by EP2-EP4/cAMP/PKA pathway.
authors.affiliation: 1 Department of Biological Science, School of Pharmaceutical Science, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil.
authors.forename: Ana Cg
authors.initials: AC
authors.lastname: Salina
authors.affiliation: 1 Department of Biological Science, School of Pharmaceutical Science, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil.
authors.forename: Tais P
authors.initials: TP
authors.lastname: Souza
authors.affiliation: 2 Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Serezani
authors.affiliation: 1 Department of Biological Science, School of Pharmaceutical Science, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil.
authors.forename: Alexandra I
authors.initials: AI
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D017209:Apoptosis; D001433:Bacteriolysis; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D019169:Jurkat Cells; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000378:metabolism; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone
keywords: Efferocytosis; Streptococcus pneumoniae; alveolar macrophages; apoptotic cells; prostaglandin E2