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Treatment with lipoxin A4 improves influenza A infection outcome, induces macrophage reprogramming, anti-inflammatory and pro-resolutive responses.
Rago, Flavia; Melo, Eliza Mathias; Miller, Leigh M; Duray, Alexis M; Batista Felix, Franciel; Vago, Juliana Priscila; de Faria Gonçalves, Ana Paula; Angelo, Ana Luiza Pessoa Mendonça; Cassali, Geovanni D; de Gaetano, Monica; Brennan, Eoin; Owen, Benjamin; Guiry, Patrick; Godson, Catherine; Alcorn, John F; Teixeira, Mauro Martins.
Afiliação
  • Rago F; Department of Biochemistry and Immunology Institute of Biological Sciences, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, CEP 31.270-901, Belo Horizonte, MG, 6627, Brazil. flaviarago@gmail.com.
  • Melo EM; Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, 9127 Rangos Research Building, 4401 Penn Ave, Pittsburgh, PA, 15224, USA. flaviarago@gmail.com.
  • Miller LM; Department of Biochemistry and Immunology Institute of Biological Sciences, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos, CEP 31.270-901, Belo Horizonte, MG, 6627, Brazil.
  • Duray AM; Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, 9127 Rangos Research Building, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.
  • Batista Felix F; Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, 9127 Rangos Research Building, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.
  • Vago JP; Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • de Faria Gonçalves AP; Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • Angelo ALPM; Immunology of Viral Diseases, René Rachou Research Center, Oswaldo Cruz Foundation (FIOCRUZ-Minas), Belo Horizonte, MG, Brazil.
  • Cassali GD; Immunology of Viral Diseases, René Rachou Research Center, Oswaldo Cruz Foundation (FIOCRUZ-Minas), Belo Horizonte, MG, Brazil.
  • de Gaetano M; Comparative Pathology Laboratory, Department of Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
  • Brennan E; School of Medicine/School of Biomolecular and Biomedical Science, UCD Diabetes Complications Research Centre, UCD Conway Institute, University College Dublin, Dublin, Ireland.
  • Owen B; School of Medicine/School of Biomolecular and Biomedical Science, UCD Diabetes Complications Research Centre, UCD Conway Institute, University College Dublin, Dublin, Ireland.
  • Guiry P; Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Dublin, Ireland.
  • Godson C; Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Dublin, Ireland.
  • Alcorn JF; School of Medicine/School of Biomolecular and Biomedical Science, UCD Diabetes Complications Research Centre, UCD Conway Institute, University College Dublin, Dublin, Ireland.
  • Teixeira MM; Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, 9127 Rangos Research Building, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.
Inflamm Res ; 2024 Aug 30.
Article em En | MEDLINE | ID: mdl-39214890
ABSTRACT

INTRODUCTION:

Influenza A is a virus from the Orthomixoviridae family responsible for high lethality rates and morbidity, despite clinically proven vaccination strategies and some anti-viral therapies. The eicosanoid Lipoxin A4 (LXA4) promotes the resolution of inflammation by decreasing cell recruitment and pro-inflammatory cytokines release, but also for inducing activation of apoptosis, efferocytosis, and macrophage reprogramming.

OBJECTIVE:

Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model.

METHOD:

Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7 µg/kg/day, i.p.) at day 3 post-infection.

RESULTS:

AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in fpr2/3 -/- animals. In mice treated with LXA4 (50 µg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of T helper 2 cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice.

CONCLUSION:

Therefore, treatment with a lipoxin A4 analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Inflamm Res Assunto da revista: ALERGIA E IMUNOLOGIA / PATOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Inflamm Res Assunto da revista: ALERGIA E IMUNOLOGIA / PATOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Brasil País de publicação: Suíça