Activation of M1/M2 Macrophages by efferocytosis of infected apoptotic cells

• Grant number: 17/04786-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2017
• End date: June 30, 2020
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Alexandra Ivo de Medeiros
• Grantee: Ana Carolina Guerta Salina
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 18/01622-9 - LTB4 actions in infected apoptotic cells clearance during Staphylococcus aureus skin infection in diabetic mice., BE.EP.DR

Abstract

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 importantfor 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. To date, there is not enough knowledge about the effect of phagocytosis of infected and uninfected apoptotic cells on the differentiation of these subpopulations 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 by our group suggest that phagocytosis of different sources of infectedapoptotic 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. (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)

GUERTA SALINA, ANA CAROLINA; BRANDT, STEPHANIE L.; KLOPFENSTEIN, NATHAN; BLACKMAN, AMONDREA; RIBEIRO BAZZANO, JULIA MIRANDA; SA-NUNES, ANDERSON; BYERS-GLOSSON, NICOLE; BRODSKYN, CLAUDIA; TAVARES, NATALIA MACHADO; SANTOS DA SILVA, ICARO BONYEK; et al. Leukotriene B-4 licenses inflammasome activation to enhance skin host defense. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 117, n. 48, p. 30619-30627, DEC 1 2020. (17/19870-6, 17/04786-0, 19/10839-4, 18/01622-9)

SALINA, ANA CAROLINA GUERTA; PENTEADO, LETICIA DE AQUINO; DEJANI, NAIARA NAIANA; SILVA-PEREIRA, LUDMILLA; RAIMUNDO, BRENO VILAS BOAS; CORREA, GABRIEL FERRANTI; OLIVEIRA, KAREN CRISTINA; RAMALHO, LEANDRA NAIRA ZAMBELLI; BOKO, MEDETON MAHOUSSI MICHAEL; BONATO, VANIA L. D.; et al. Different bacterial cargo in apoptotic cells drive distinct macrophage phenotypes. Apoptosis, v. N/A, p. 10-pg., 2023-10-05. (11/17611-7, 12/23580-0, 20/09327-6, 17/21629-5, 16/10964-5, 18/19638-9, 17/04786-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SALINA, Ana Carolina Guerta. M1/M2 macrophage activation by efferocytosis of infectedapoptotic cells. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.