Evaluation of macrophage polarization in cultures with Schwann cells infected with Mycobacterium leprae.

Author(s)

Bruna Beatriz Gimenez Carra

• Document type: Master's Dissertation
• Press: Botucatu. 2018-11-26.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu
• Defense date: 2018-10-26
• Advisor: Vânia Niéto Brito de Souza; Maria Renata Sales Nogueira

Abstract

Mycobacterium leprae (ML) infection stimulates dedifferentiation and proliferation of Schwann cells (SCs) that may contribute to the spread of the bacillus. Macrophages (MOs) are effector cells of the immune response that promote the elimination of pathogens, however, in leprosy they are colonized by ML. It is known that MOs can present a functional polarization in which M1 MOs show pro-inflammatory and microbicidal activities while M2 MOs act in tissue repair presenting an anti-inflammatory profile. SCs infected by ML produce mediators able to interfere with MOs function, increasing their survival and promoting their migration. Although different functional programs have been observed in MOs from patients with polar forms of leprosy, the influence of SCs in this process is not known. In this study we evaluated whether SCs infected with ML could interfere in the polarization of murine MOs derived from bone marrow. For this purpose, primary cultures of murine SCs were experimentally infected with viable bacilli and co-cultivated with MOs. Our results indicate that nitric oxide production was low in cultures of MOs after infection with the bacillus, but it was increased in the co-cultures of MOs and ML-infected SCs. The infection with ML did not induce significant production of IL-10, TNF and IL-6 in cultures of MOs and SCs, however, the interaction between MOs and ML infected-SCs resulted in increased production of cytokines, mainly IL-10, inducing a decrease in the TNF/IL-10 ratio. In addition, we observed a decrease in the expression of M1 markers (CD86 and iNOS) and an increase in the expression of the CD206, a marker of M2 MOs. In conclusion, ML infection of SCs is able to interfere with polarization of MOs resulting in a M2-like profile by inducing the occurrence of an anti-inflammatory environment. (AU)

• FAPESP's process: 16/16073-5 - Evaluation of macrophages polarization of in cocultures with Schwann cells infected by Mycobacterium leprae
• Grantee: Bruna Beatriz de Oliveira Gimenez
• Support Opportunities: Scholarships in Brazil - Master