GILZ Modulates the Recruitment of Monocytes/Macrophages Endowed with a Resolving Phenotype and Favors Resolution of <i>Escherichia coli</i> Infection
Laís C. Grossi,
Isabella Zaidan,
Jéssica Amanda Marques Souza,
Antônio Felipe S. Carvalho,
Rodrigo C. O. Sanches,
Camila Cardoso,
Edvaldo S. Lara,
Ana Clara M. Montuori-Andrade,
Stefano Bruscoli,
Maria Cristina Marchetti,
Carlo Riccardi,
Mauro M. Teixeira,
Luciana P. Tavares,
Juliana P. Vago,
Lirlândia P. Sousa
Affiliations
Laís C. Grossi
Signaling in Inflammation Lab., Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
Isabella Zaidan
Signaling in Inflammation Lab., Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
Jéssica Amanda Marques Souza
Signaling in Inflammation Lab., Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
Antônio Felipe S. Carvalho
Signaling in Inflammation Lab., Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
Rodrigo C. O. Sanches
Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
Camila Cardoso
Signaling in Inflammation Lab., Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
Edvaldo S. Lara
Signaling in Inflammation Lab., Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
Ana Clara M. Montuori-Andrade
Signaling in Inflammation Lab., Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
Stefano Bruscoli
Department of Medicine and Surgery, Section of Pharmacology, University of Perugia, 06132 Perugia, Italy
Maria Cristina Marchetti
Department of Medicine and Surgery, Section of Pharmacology, University of Perugia, 06132 Perugia, Italy
Carlo Riccardi
Department of Medicine and Surgery, Section of Pharmacology, University of Perugia, 06132 Perugia, Italy
Mauro M. Teixeira
Centro de Pesquisa e Desenvolvimento de Fármacos, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
Luciana P. Tavares
Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Juliana P. Vago
Experimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Lirlândia P. Sousa
Signaling in Inflammation Lab., Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil
Macrophages are important effectors of inflammation resolution that contribute to the elimination of pathogens and apoptotic cells and restoration of homeostasis. Pre-clinical studies have evidenced the anti-inflammatory and pro-resolving actions of GILZ (glucocorticoid-induced leucine zipper). Here, we evaluated the role of GILZ on the migration of mononuclear cells under nonphlogistic conditions and Escherichia coli-evoked peritonitis. TAT-GILZ (a cell-permeable GILZ-fusion protein) injection into the pleural cavity of mice induced monocyte/macrophage influx alongside increased CCL2, IL-10 and TGF-β levels. TAT-GILZ-recruited macrophages showed a regulatory phenotype, exhibiting increased expression of CD206 and YM1. During the resolving phase of E. coli-induced peritonitis, marked by an increased recruitment of mononuclear cells, lower numbers of these cells and CCL2 levels were found in the peritoneal cavity of GILZ-deficient mice (GILZ−/−) when compared to WT. In addition, GILZ−/− showed higher bacterial loads, lower apoptosis/efferocytosis counts and a lower number of macrophages with pro-resolving phenotypes. TAT-GILZ accelerated resolution of E. coli-evoked neutrophilic inflammation, which was associated with increased peritoneal numbers of monocytes/macrophages, enhanced apoptosis/efferocytosis counts and bacterial clearance through phagocytosis. Taken together, we provided evidence that GILZ modulates macrophage migration with a regulatory phenotype, inducing bacterial clearance and accelerating the resolution of peritonitis induced by E. coli.
