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Glucocorticoid-Induced Leucine Zipper Alleviates Lung Inflammation and Enhances Bacterial Clearance during Pneumococcal Pneumonia

Authors :
Jéssica Amanda Marques Souza
Antônio Felipe S. Carvalho
Lais C. Grossi
Isabella Zaidan
Leonardo Camilo de Oliveira
Juliana P. Vago
Camila Cardoso
Marina G. Machado
Geovanna V. Santos Souza
Celso Martins Queiroz-Junior
Eric F. Morand
Stefano Bruscoli
Carlo Riccardi
Mauro M. Teixeira
Luciana P. Tavares
Lirlândia P. Sousa
Source :
Cells, Vol 11, Iss 3, p 532 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Pneumonia is a leading cause of morbidity and mortality. While inflammation is a host protective response that ensures bacterial clearance, a finely regulated response is necessary to prevent bystander tissue damage. Glucocorticoid (GC)-induced leucine zipper (GILZ) is a GC-induced protein with anti-inflammatory and proresolving bioactions, yet the therapeutical role of GILZ in infectious diseases remains unexplored. Herein, we investigate the role and effects of GILZ during acute lung injury (ALI) induced by LPS and Streptococcus pneumoniae infection. GILZ deficient mice (GILZ−/−) presented more severe ALI, characterized by increased inflammation, decreased macrophage efferocytosis and pronounced lung damage. In contrast, pulmonary inflammation, and damage were attenuated in WT mice treated with TAT-GILZ fusion protein. During pneumococcal pneumonia, TAT-GILZ reduced neutrophilic inflammation and prevented the associated lung damage. There was also enhanced macrophage efferocytosis and bacterial clearance in TAT-GILZ-treated mice. Mechanistically, TAT-GILZ enhanced macrophage phagocytosis of pneumococcus, which was lower in GILZ−/− macrophages. Noteworthy, early treatment with TAT-GILZ rescued 30% of S. pneumoniae-infected mice from lethal pneumonia. Altogether, we present evidence that TAT-GILZ enhances host resilience and resistance to pneumococcal pneumonia by controlling pulmonary inflammation and bacterial loads leading to decreased lethality. Exploiting GILZ pathways holds promise for the treatment of severe respiratory infections.

Details

Language :
English
ISSN :
20734409
Volume :
11
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Cells
Publication Type :
Academic Journal
Accession number :
edsdoj.3ba69f7bc349109acf0c6819ea48d9
Document Type :
article
Full Text :
https://doi.org/10.3390/cells11030532