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Effect of phagocytosis of infected apoptotic cells during activation of M1/M2 macrophages

Grant number: 17/19870-6
Support type:Regular Research Grants
Duration: February 01, 2018 - June 30, 2020
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Alexandra Ivo de Medeiros
Grantee:Alexandra Ivo de Medeiros
Home Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil


Infectious conditions are characterized by intense migration of cells such as neutrophils and monocytes, to the infected tissue in an attempt to contain the bacterial proliferation. After the phagocytosis of microorganisms, these cells eventually die, resulting in an accumulation of infected apoptotic cells in the tissue. The phagocytosis of infected apoptotic cells, called efferocytosis, is an essential and dynamic process for the homeostasis of tissues after injury. Phagocytes, such as macrophages, are important for the defense against microorganisms and are also involved in the clearance these apoptotic cells. There are two populations of macrophages, M1 (pro-inflammatory) and M2 (anti-inflammatory) that differ in the state of activation and immunological function, in response to the interaction with antigenic stimuli and/or soluble factors present in the microenvironment. However, so far, there is not study about the effect of phagocytosis of infected and uninfected apoptotic cells during activation of M1/M2 macrophages. It is known that phagocytosis of sterile apoptotic cells by peritoneal macrophages and macrophage lineage leads to inhibition of iNOS and TNF-± expression and increased of expression of Arginase-1, IL-4, IL-13, IL-10 and TGF-², leading to a M2 polarization profile. On the other hand, preliminary data obtained from our group suggest that phagocytosis of different sources of infected apoptotic cells, Streptococcus pneumoniae or Escherichia coli, results in the differentiation of macrophages with mixed profile (M1/M2) and M1, respectively. Therefore, the hypothesis of this study is that phagocytosis of infected apoptotic cells with Gram-positive and -negative bacteria triggers a distinct regulation of SOCS protein that will influence in the M1/M2 macrophage activation in a manner dependent of STAT transcription factors.Keywords: M1/M2 macrophages, efferocytosis, Streptococcus pneumoniae, Klebsiella pneumoniae, apoptotic cells, transcription factors (AU)

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)
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, MAR 1 2020. Web of Science Citations: 0.
CODO, ANA CAMPOS; SARAIVA, AMANDA CORREIA; DOS SANTOS, LEONARDO LIMA; VISCONDE, MARINA FRANCISCO; GALES, ANA CRISTINA; ZAMBONI, DARIO SIMOES; MEDEIROS, ALEXANDRA IVO. Inhibition of inflammasome activation by a clinical strain of Klebsiella pneumoniae impairs efferocytosis and leads to bacterial dissemination. CELL DEATH & DISEASE, v. 9, DEC 5 2018. Web of Science Citations: 3.

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