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The Therapeutic Treatment with the GAG-Binding Chemokine Fragment CXCL9(74–103) Attenuates Neutrophilic Inflammation and Lung Dysfunction during Klebsiella pneumoniae Infection in Mice

Klebsiella pneumoniae is an important pathogen associated with hospital-acquired pneumonia (HAP). Bacterial pneumonia is characterized by a harmful inflammatory response with a massive influx of neutrophils, production of cytokines and chemokines, and consequent tissue damage and dysfunction. Target...

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Autores principales: Boff, Daiane, Russo, Remo Castro, Crijns, Helena, de Oliveira, Vivian Louise Soares, Mattos, Matheus Silvério, Marques, Pedro Elias, Menezes, Gustavo Batista, Vieira, Angélica Thomaz, Teixeira, Mauro Martins, Proost, Paul, Amaral, Flávio Almeida
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181286/
https://www.ncbi.nlm.nih.gov/pubmed/35682923
http://dx.doi.org/10.3390/ijms23116246
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author Boff, Daiane
Russo, Remo Castro
Crijns, Helena
de Oliveira, Vivian Louise Soares
Mattos, Matheus Silvério
Marques, Pedro Elias
Menezes, Gustavo Batista
Vieira, Angélica Thomaz
Teixeira, Mauro Martins
Proost, Paul
Amaral, Flávio Almeida
author_facet Boff, Daiane
Russo, Remo Castro
Crijns, Helena
de Oliveira, Vivian Louise Soares
Mattos, Matheus Silvério
Marques, Pedro Elias
Menezes, Gustavo Batista
Vieira, Angélica Thomaz
Teixeira, Mauro Martins
Proost, Paul
Amaral, Flávio Almeida
author_sort Boff, Daiane
collection PubMed
description Klebsiella pneumoniae is an important pathogen associated with hospital-acquired pneumonia (HAP). Bacterial pneumonia is characterized by a harmful inflammatory response with a massive influx of neutrophils, production of cytokines and chemokines, and consequent tissue damage and dysfunction. Targeted therapies to block neutrophil migration to avoid tissue damage while keeping the antimicrobial properties of tissue remains a challenge in the field. Here we tested the effect of the anti-inflammatory properties of the chemokine fragment CXCL9(74–103) in pneumonia induced by Klebsiella pneumoniae in mice. Mice were infected by intratracheal injection of Klebsiella pneumoniae and 6 h after infection were treated systemically with CXCL9(74–103). The recruitment of leukocytes, levels of cytokines and chemokines, colony-forming units (CFU), and lung function were evaluated. The treatment with CXCL9(74–103) decreased neutrophil migration to the airways and the production of the cytokine interleukin-1β (IL-1β) without affecting bacterial control. In addition, the therapeutic treatment improved lung function in infected mice. Our results indicated that the treatment with CXCL9(74–103) reduced inflammation and improved lung function in Klebsiella pneumoniae-induced pneumonia.
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spelling pubmed-91812862022-06-10 The Therapeutic Treatment with the GAG-Binding Chemokine Fragment CXCL9(74–103) Attenuates Neutrophilic Inflammation and Lung Dysfunction during Klebsiella pneumoniae Infection in Mice Boff, Daiane Russo, Remo Castro Crijns, Helena de Oliveira, Vivian Louise Soares Mattos, Matheus Silvério Marques, Pedro Elias Menezes, Gustavo Batista Vieira, Angélica Thomaz Teixeira, Mauro Martins Proost, Paul Amaral, Flávio Almeida Int J Mol Sci Article Klebsiella pneumoniae is an important pathogen associated with hospital-acquired pneumonia (HAP). Bacterial pneumonia is characterized by a harmful inflammatory response with a massive influx of neutrophils, production of cytokines and chemokines, and consequent tissue damage and dysfunction. Targeted therapies to block neutrophil migration to avoid tissue damage while keeping the antimicrobial properties of tissue remains a challenge in the field. Here we tested the effect of the anti-inflammatory properties of the chemokine fragment CXCL9(74–103) in pneumonia induced by Klebsiella pneumoniae in mice. Mice were infected by intratracheal injection of Klebsiella pneumoniae and 6 h after infection were treated systemically with CXCL9(74–103). The recruitment of leukocytes, levels of cytokines and chemokines, colony-forming units (CFU), and lung function were evaluated. The treatment with CXCL9(74–103) decreased neutrophil migration to the airways and the production of the cytokine interleukin-1β (IL-1β) without affecting bacterial control. In addition, the therapeutic treatment improved lung function in infected mice. Our results indicated that the treatment with CXCL9(74–103) reduced inflammation and improved lung function in Klebsiella pneumoniae-induced pneumonia. MDPI 2022-06-02 /pmc/articles/PMC9181286/ /pubmed/35682923 http://dx.doi.org/10.3390/ijms23116246 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Boff, Daiane
Russo, Remo Castro
Crijns, Helena
de Oliveira, Vivian Louise Soares
Mattos, Matheus Silvério
Marques, Pedro Elias
Menezes, Gustavo Batista
Vieira, Angélica Thomaz
Teixeira, Mauro Martins
Proost, Paul
Amaral, Flávio Almeida
The Therapeutic Treatment with the GAG-Binding Chemokine Fragment CXCL9(74–103) Attenuates Neutrophilic Inflammation and Lung Dysfunction during Klebsiella pneumoniae Infection in Mice
title The Therapeutic Treatment with the GAG-Binding Chemokine Fragment CXCL9(74–103) Attenuates Neutrophilic Inflammation and Lung Dysfunction during Klebsiella pneumoniae Infection in Mice
title_full The Therapeutic Treatment with the GAG-Binding Chemokine Fragment CXCL9(74–103) Attenuates Neutrophilic Inflammation and Lung Dysfunction during Klebsiella pneumoniae Infection in Mice
title_fullStr The Therapeutic Treatment with the GAG-Binding Chemokine Fragment CXCL9(74–103) Attenuates Neutrophilic Inflammation and Lung Dysfunction during Klebsiella pneumoniae Infection in Mice
title_full_unstemmed The Therapeutic Treatment with the GAG-Binding Chemokine Fragment CXCL9(74–103) Attenuates Neutrophilic Inflammation and Lung Dysfunction during Klebsiella pneumoniae Infection in Mice
title_short The Therapeutic Treatment with the GAG-Binding Chemokine Fragment CXCL9(74–103) Attenuates Neutrophilic Inflammation and Lung Dysfunction during Klebsiella pneumoniae Infection in Mice
title_sort therapeutic treatment with the gag-binding chemokine fragment cxcl9(74–103) attenuates neutrophilic inflammation and lung dysfunction during klebsiella pneumoniae infection in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181286/
https://www.ncbi.nlm.nih.gov/pubmed/35682923
http://dx.doi.org/10.3390/ijms23116246
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