Extracellular mycobacterial DnaK polarizes macrophages to the M2-like phenotype

• Autor(a) principal: Lopes, Rafael Lisboa
• Data de Publicação: 2014
• Outros Autores: Borges, Thiago de Jesus, Araujo, Jessica Fonseca de, Pinho, Nathana Gustavo, Bergamin, Letícia Scussel, Battastini, Ana Maria Oliveira, Muraro, Stéfanie Primon, Souza, Ana Paula de, Zanin, Rafael Fernandes, Bonorino, Cristina Beatriz Cazabuena
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/225487
• topic: Macrófagos; Mycobacterium tuberculosis; Fenótipo; Proteínas de choque térmico HSP70

Macrophages are myeloid cells that play an essential role in inflammation and host defense, regulating immune responses and maintaining tissue homeostasis. Depending on the microenvironment, macrophages can polarize to two distinct phenotypes. The M1 phenotype is activated by IFN-c and bacterial products, and displays an inflammatory profile, while M2 macrophages are activated by IL-4 and tend to be anti-inflammatory or immunosupressive. It was observed that DnaK from Mycobacterium tuberculosis has immunosuppressive properties, inducing a tolerogenic phenotype in dendritic cells and MDSCs, contributing to graft acceptance and tumor growth. However, its role in macrophage polarization remains to be elucidated. We asked whether DnaK was able to modulate macrophage phenotype. Murine macrophages, derived from bone marrow, or from the peritoneum, were incubated with DnaK and their phenotype compared to M1 or M2 polarized macrophages. Treatment with DnaK leads macrophages to present higher arginase I activity, IL-10 production and FIZZ1 and Ym1 expression. Furthermore, DnaK increased surface levels of CD206. Importantly, DnaK-treated macrophages were able to promote tumor growth in an allogeneic melanoma model. Our results suggest that DnaK polarizes macrophages to the M2-like phenotype and could constitute a virulence factor and is an important immunomodulator of macrophage responses.