Impact of eferocytosis in microbicidal activity of alveolar macrophages via receptors " scavenger": role of prostaglandin E2

• Grant number: 11/23979-7
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2012
• Effective date (End): December 31, 2012
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal researcher: Alexandra Ivo de Medeiros
• Grantee: Ana Carolina Guerta Salina
• Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

The ingestion of non-infected apoptotic cells by phagocytes (termed efferocytosis) results in suppression of the innate immune response and Treg cell differentiation. This occurs through the release of antiinflammatory mediators such as IL-10, TGF-², prostaglandin E2 (PGE2) by phagocytes as a result of the Cell surface receptors and their ligands in apoptotic cells.Lipid mediators play an important role in innate and acquired immune response against infectious agents. PGE2, through the interaction of EP2 and EP4 receptors, inhibits phagocytosis and microbicidal activity of microorganisms opsonized with IgG in alveolar macrophages (AMs). The molecular and cellular mechanisms that PGE2 interferes with the effector functions of AMs are great clinical relevance for prevention and intervention process or suppression of the immune response against intracellular pathogens. The inhibitory effect of PGE 2 on phagocytosis and microbicidal activity of AMs via the Fc receptor has been extensively studied. However, the role of PGE2 in the effector functions of AMs via receptors of the innate immune response, as receiver "scavenger", it is still unknown.Recently we demonstrated that the instillation of apoptotic cells in uninfected mice promotes the PGE2 synthesis that through interaction with EP2 receptor, increases the synthesis of IL-10 and prevents the elimination of Streptococcus pneumoniae in the lung. The absence of antibodies against S. pneumoniae in the lungs of these mice suggest that PGE2, in addition to modulate the effector functions mediated by Fc receptors in AMs, may also play an important role in the innate immune response by other ligands such as scavenger receptors, complement and toll -like receptors.Thus, the aim of the present study is to examine whether PGE2 secreted during the efferocytosis by AMs may interfere in the process of microbicidal activity against S. pneumoniae, via receptors "scavenger".

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SALINA, ANA C. G.; SOUZA, TAIS P.; SEREZANI, CARLOS H.; MEDEIROS, ALEXANDRA I. Efferocytosis-induced prostaglandin E2 production impairs alveolar macrophage effector functions during Streptococcus pneumoniae infection. Innate Immunity, v. 23, n. 3, p. 219-227, APR 2017. Web of Science Citations: 3.