M1/M2 macrophage activation by efferocytosis of infectedapoptotic cells

Author(s)

Ana Carolina Guerta Salina

• Document type: Doctoral Thesis
• Press: Ribeirão Preto.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC)
• Defense date: 2020-06-05

Examining board members

Alexandra Ivo de Medeiros; Karina Ramalho Bortoluci; Larissa Dias da Cunha

• Advisor: Alexandra Ivo de Medeiros

Abstract

During infectious processes, there is intense recruitment of phagocytes, such as neutrophils and monocytes to the affected tissue, in an attempt to contain bacterial proliferation. These cells, after exercising their effector functions, enter cell death process, resulting in an intense accumulation of infected-apoptotic cells in the tissue. The phagocytosis of these apoptotic cells, called efferocytosis, is a dynamic process of fundamental importance for tissue homeostasis, thereby preventing tissue necrosis. Among these phagocytes, macrophages are important both in the defense against microorganisms and the removal of these apoptotic cells. There are at least two populations of macrophages that differ in terms of activation status and immune function. M1 macrophages are pro-inflammatory and specialized in controlling infections, while M2 macrophages are anti-inflammatory and are related to tissue repair. To date, little is known about the effect of phagocytosis of infected and sterile apoptotic cells on the differentiation of these subpopulations of M1 / M2 macrophages. Here, we demonstrated that the efferocytosis of Streptococcus pneumoniae-infected apoptotic cells (AC-Sp) induces a mixed polarization profile dependent on the signaling pathways triggered by the TLR2 and TLR4 receptors, activation of NF-κB, STAT1 and STAT3 transcription factors and caspase 11. On the other hand, the efferocytosis of of Klebsiella pneumoniae-infected apoptotic cells (ACKp) induces the activation of M1 profile dependent on NF-κB and STAT1. In vivo, the challenge with AC-Sp induces a less inflammatory microenvironment, while the challenge with AC-Kp results in the production of both inflammatory and antiinflammatory mediators in the pulmonary microenvironment.This study contributes to the understanding of how efferocytosis of infected-apoptotic cells by different bacterias can directly regular the macrophage activation and differentiation in M1/M2 profile and effector functions both in resolving the infection and in restoring tissue homeostasis. (AU)

• FAPESP's process: 17/04786-0 - Activation of M1/M2 Macrophages by efferocytosis of infected apoptotic cells
• Grantee: Ana Carolina Guerta Salina
• Support Opportunities: Scholarships in Brazil - Doctorate