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Efferocytosis of Streptococcus pneumoniae infected apoptotic cells impact on m2 macrophages and Th2 lymphocytes reprogramming

Grant number: 17/18807-9
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2018
Effective date (End): January 31, 2019
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Alexandra Ivo de Medeiros
Grantee:Ana Campos Codo
Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


The phagocytosis of apoptotic cells (ACs) - called efferocytosis - is an essential process in the maintenance of tissue homeostasis. Macrophages, which collaborate in the defense against microorganisms, also play an important role in ACs removal. Depending on the microenvironment and aggressor agents presented in the tissue, there are at least two macrophages populations that differ in phenotype and effector functions - M1 (proinflammatory) and M2 (anti-inflammatory) macrophages. It is well described that ACs phagocytosis by M0 macrophages promotes a macrophage activation towards a M2 profile. However, recent data obtained by our research group demonstrated that M0 macrophages co-cultivated in the presence of Streptococcus pneumoniae infected apoptotic cell (iAC) presented a mixed M1/M2 profile, capable of producing both IL-6 and TGF-², and IL-12. During a pulmonary chronic allergic inflammation, there is a predominance of M2 macrophages, Th2 lymphocytes and eosinophils. Nevertheless, individuals affected by this chronic allergic inflammation are more susceptible to pneumoniae, specially the one caused by S. pneumoniae. During the infectious process, there is an intense accumulation of infected neutrophil in the lung, favoring the development of a neutrophil asthma together with predominance of neutrophils and Th17 lymphocytes, that are associated with more severe cases of the disease. In both inflammatory process, there is a huge accumulation of eosinophils and infected neutrophils which become apoptotic cell and are phagocyted by macrophages. The difference in the cytokines profiles produced during the efferocytosis of ACs, in the absence or presence of microorganism, could generate a microenvironment able to reprogram the lymphocytes and macrophages phenotypes. Therefore, using the principal cellular components involved in the pulmonary chronic allergic inflammation in the presence of an infectious process to an in vitro study, the hypothesis of this study is that the phagocytosis of apoptotic eosinophils by macrophages would assist in the maintenance of a M2 macrophages and Th2 lymphocytes profiles. However, in the presence of an infectious agent, such as S. pneumoniae, the intense apoptotic infected neutrophils accumulation would be phagocyted by these M2 macrophages, favoring a reprogramming of these macrophages to a M1 profile, as well as the Th2 plasticity to a Th17 profile. (AU)

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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)
RIBEIRO, DAYANE C.; RUSSO, HELENA M.; FRAIGE, KARINA; ZERAIK, MARIA L.; NOGUEIRA, CLAUDIO R.; DA SILVA, PATRICIA B.; CODO, ANA C.; CALIXTO, GIOVANA M. F.; DE MEDEIROS, ALEXANDRA I.; CHORILLI, MARLUS; et al. Bioactive Biofllavonoids from Platonia insignis (Bacuri) Residues as Added Value Compounds. Journal of the Brazilian Chemical Society, v. 32, n. 4, p. 786-799, . (16/16970-7, 17/18807-9, 14/50926-0, 17/19870-6, 13/07600-3)
DAYANE C. RIBEIRO; HELENA M. RUSSO; KARINA FRAIGE; MARIA L. ZERAIK; CLÁUDIO R. NOGUEIRA; PATRÍCIA B. DA SILVA; ANA C. CODO; GIOVANA M. F. CALIXTO; ALEXANDRA I. DE MEDEIROS; MARLUS CHORILLI; et al. Bioactive Bioflavonoids from Platonia insignis (Bacuri) Residues as Added Value Compounds. Journal of the Brazilian Chemical Society, v. 32, n. 4, p. 786-799, . (17/19870-6, 13/07600-3, 16/16970-7, 17/18807-9, 14/50926-0)
QUEIROZ, SUZANA APARECIDA S.; PINTO, MERI EMILI F.; BOBEY, ANTONIO F.; RUSSO, HELENA M.; BATISTA, ANDREA N. L.; BATISTA, JR., JOAO M.; CODO, ANA C.; MEDEIROS, ALEXANDRA I.; BOLZANI, VANDERLAN S.. Diterpenoids with inhibitory activity of nitrite production from Croton floribundus. Journal of Ethnopharmacology, v. 249, . (19/04381-5, 13/07600-3, 14/25222-9, 17/19870-6, 17/18807-9, 14/50926-0, 17/17098-4)

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