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- Title
GILZ Modulates the Recruitment of Monocytes/Macrophages Endowed with a Resolving Phenotype and Favors Resolution of Escherichia coli Infection.
- Authors
Grossi, Laís C.; Zaidan, Isabella; Souza, Jéssica Amanda Marques; Carvalho, Antônio Felipe S.; Sanches, Rodrigo C. O.; Cardoso, Camila; Lara, Edvaldo S.; Montuori-Andrade, Ana Clara M.; Bruscoli, Stefano; Marchetti, Maria Cristina; Riccardi, Carlo; Teixeira, Mauro M.; Tavares, Luciana P.; Vago, Juliana P.; Sousa, Lirlândia P.
- Abstract
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.
- Subjects
PHAGOCYTOSIS; ESCHERICHIA coli diseases; MONOCYTES; MACROPHAGES; CELL migration; ESCHERICHIA coli
- Publication
Cells (2073-4409), 2023, Vol 12, Issue 10, p1403
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells12101403