Extracellular Mycobacterial DnaK Polarizes Macrophages to the M2-Like Phenotype

• DOI: 10.1371/journal.pone.0113441
• Publication Date: 2014-11-24T18:50:12Z
• Authors: Rafael L. Lopes; Thiago J. Borges; Jessica F. Araújo; Nathana G. Pinho; Letícia S. Bergamin; Ana Maria O. Batt...; Stéfanie P. Muraro; Ana Paula D. Souza; Rafael F. Zanin; Cristina Bonorino
• Keywords: Macrophage polarization

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