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

Autor(es)

Salina, Ana C. G. ; Souza, Tais P. ; Serezani, Carlos H. ; Medeiros, Alexandra I.

• Tipo de documento: Artigo Científico
• Fonte: Innate Immunity; v. 23, n. 3, p. 219-227, APR 2017.
• Citações Web of Science: 3

Resumo

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(2)) 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(2) production, activation of the EP2-EP4/cAMP/PKA pathway and inhibition of H2O2 production. Our data suggest that the PGE(2) produced by AMs during efferocytosis inhibits H2O2 production and impairs the efficient clearance non-opsonized S. pneumoniae by EP2-EP4/cAMP/PKA pathway. (AU)

• Processo FAPESP: 11/23979-7 - Impacto da eferocitose na atividade microbicida via receptores scavenger em macrófagos alveolares: papel de prostaglandina E2
• Beneficiário: Ana Carolina Guerta Salina
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 11/17611-7 - Efeito da fagocitose de células apoptóticas por células dendríticas na diferenciação de células Th17: função de PGE2
• Beneficiário: Alexandra Ivo de Medeiros
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores