{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:02:03Z","timestamp":1790121723288,"version":"4.0.1"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Science and Technology in Dengue and host-microbial interactions","award":["465425\/2014-3"],"award-info":[{"award-number":["465425\/2014-3"]}]},{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ-03221-18"],"award-info":[{"award-number":["APQ-03221-18"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["PQ-306789\/2018\/3"],"award-info":[{"award-number":["PQ-306789\/2018\/3"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["23038.003950\/2020-16"],"award-info":[{"award-number":["23038.003950\/2020-16"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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\u2212\/\u2212) 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\u2212\/\u2212 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.<\/jats:p>","DOI":"10.3390\/cells11030532","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T11:35:17Z","timestamp":1643974517000},"page":"532","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Glucocorticoid-Induced Leucine Zipper Alleviates Lung Inflammation and Enhances Bacterial Clearance during Pneumococcal Pneumonia"],"prefix":"10.3390","volume":"11","author":[{"given":"J\u00e9ssica Amanda Marques","family":"Souza","sequence":"first","affiliation":[{"name":"Signaling in Inflammation Laboratory, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6185-274X","authenticated-orcid":false,"given":"Ant\u00f4nio Felipe S.","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Signaling in Inflammation Laboratory, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lais C.","family":"Grossi","sequence":"additional","affiliation":[{"name":"Signaling in Inflammation Laboratory, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9434-8814","authenticated-orcid":false,"given":"Isabella","family":"Zaidan","sequence":"additional","affiliation":[{"name":"Signaling in Inflammation Laboratory, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7393-5013","authenticated-orcid":false,"given":"Leonardo Camilo","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa e Desenvolvimento de F\u00e1rmacos, Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana P.","family":"Vago","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology, Department of Rheumatology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8131-579X","authenticated-orcid":false,"given":"Camila","family":"Cardoso","sequence":"additional","affiliation":[{"name":"Signaling in Inflammation Laboratory, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-613X","authenticated-orcid":false,"given":"Marina G.","family":"Machado","sequence":"additional","affiliation":[{"name":"Signaling in Inflammation Laboratory, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"},{"name":"Centro de Pesquisa e Desenvolvimento de F\u00e1rmacos, Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geovanna V. Santos","family":"Souza","sequence":"additional","affiliation":[{"name":"Signaling in Inflammation Laboratory, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celso Martins","family":"Queiroz-Junior","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa e Desenvolvimento de F\u00e1rmacos, Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9507-3338","authenticated-orcid":false,"given":"Eric F.","family":"Morand","sequence":"additional","affiliation":[{"name":"Rheumatology Group, Centre for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Monash University, Melbourne 3168, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0313-1615","authenticated-orcid":false,"given":"Stefano","family":"Bruscoli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Section of Pharmacology, University of Perugia, 06156 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9257-3997","authenticated-orcid":false,"given":"Carlo","family":"Riccardi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Section of Pharmacology, University of Perugia, 06156 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro M.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Centro de Pesquisa e Desenvolvimento de F\u00e1rmacos, Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5319-0210","authenticated-orcid":false,"given":"Luciana P.","family":"Tavares","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1042-9762","authenticated-orcid":false,"given":"Lirl\u00e2ndia P.","family":"Sousa","sequence":"additional","affiliation":[{"name":"Signaling in Inflammation Laboratory, Departamento de An\u00e1lises Cl\u00ednicas e Toxicol\u00f3gicas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Ci\u00eancias Farmac\u00eauticas, Faculdade de Farm\u00e1cia, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"},{"name":"Centro de Pesquisa e Desenvolvimento de F\u00e1rmacos, Departamento de Bioqu\u00edmica e Imunologia, Instituto de Ci\u00eancias Biol\u00f3gicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"ref_1","unstructured":"WHO (2021, October 22). 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