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Extracellular Mycobacterial DnaK Polarizes Macrophages to the M2-Like Phenotype

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-γ and bacterial pro...

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Autores principales: Lopes, Rafael L., Borges, Thiago J., Araújo, Jessica F., Pinho, Nathana G., Bergamin, Letícia S., Battastini, Ana Maria O., Muraro, Stéfanie P., Souza, Ana Paula D., Zanin, Rafael F., Bonorino, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242626/
https://www.ncbi.nlm.nih.gov/pubmed/25419575
http://dx.doi.org/10.1371/journal.pone.0113441
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author Lopes, Rafael L.
Borges, Thiago J.
Araújo, Jessica F.
Pinho, Nathana G.
Bergamin, Letícia S.
Battastini, Ana Maria O.
Muraro, Stéfanie P.
Souza, Ana Paula D.
Zanin, Rafael F.
Bonorino, Cristina
author_facet Lopes, Rafael L.
Borges, Thiago J.
Araújo, Jessica F.
Pinho, Nathana G.
Bergamin, Letícia S.
Battastini, Ana Maria O.
Muraro, Stéfanie P.
Souza, Ana Paula D.
Zanin, Rafael F.
Bonorino, Cristina
author_sort Lopes, Rafael L.
collection PubMed
description 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-γ 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.
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spelling pubmed-42426262014-11-26 Extracellular Mycobacterial DnaK Polarizes Macrophages to the M2-Like Phenotype Lopes, Rafael L. Borges, Thiago J. Araújo, Jessica F. Pinho, Nathana G. Bergamin, Letícia S. Battastini, Ana Maria O. Muraro, Stéfanie P. Souza, Ana Paula D. Zanin, Rafael F. Bonorino, Cristina PLoS One Research Article 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-γ 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. Public Library of Science 2014-11-24 /pmc/articles/PMC4242626/ /pubmed/25419575 http://dx.doi.org/10.1371/journal.pone.0113441 Text en © 2014 Lopes et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lopes, Rafael L.
Borges, Thiago J.
Araújo, Jessica F.
Pinho, Nathana G.
Bergamin, Letícia S.
Battastini, Ana Maria O.
Muraro, Stéfanie P.
Souza, Ana Paula D.
Zanin, Rafael F.
Bonorino, Cristina
Extracellular Mycobacterial DnaK Polarizes Macrophages to the M2-Like Phenotype
title Extracellular Mycobacterial DnaK Polarizes Macrophages to the M2-Like Phenotype
title_full Extracellular Mycobacterial DnaK Polarizes Macrophages to the M2-Like Phenotype
title_fullStr Extracellular Mycobacterial DnaK Polarizes Macrophages to the M2-Like Phenotype
title_full_unstemmed Extracellular Mycobacterial DnaK Polarizes Macrophages to the M2-Like Phenotype
title_short Extracellular Mycobacterial DnaK Polarizes Macrophages to the M2-Like Phenotype
title_sort extracellular mycobacterial dnak polarizes macrophages to the m2-like phenotype
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242626/
https://www.ncbi.nlm.nih.gov/pubmed/25419575
http://dx.doi.org/10.1371/journal.pone.0113441
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