Treatment with lipoxin A 4 improves influenza A infection outcome, induces macrophage reprogramming, anti-inflammatory and pro-resolutive responses.

Autor: 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.; Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, 9127 Rangos Research Building, 4401 Penn Ave, Pittsburgh, PA, 15224, USA. flaviarago@gmail.com., Melo EM; 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., Miller LM; Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, 9127 Rangos Research Building, 4401 Penn Ave, Pittsburgh, PA, 15224, USA., 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 Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., Vago JP; Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., de Faria Gonçalves AP; Immunology of Viral Diseases, René Rachou Research Center, Oswaldo Cruz Foundation (FIOCRUZ-Minas), 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; Comparative Pathology Laboratory, Department of Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil., de Gaetano M; School of Medicine/School of Biomolecular and Biomedical Science, UCD Diabetes Complications Research Centre, UCD Conway Institute, University College Dublin, Dublin, Ireland., 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; Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Dublin, Ireland., Guiry P; Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Dublin, Ireland., Godson C; School of Medicine/School of Biomolecular and Biomedical Science, UCD Diabetes Complications Research Centre, UCD Conway Institute, University College Dublin, Dublin, Ireland., Alcorn JF; Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, 9127 Rangos Research Building, 4401 Penn Ave, Pittsburgh, PA, 15224, USA., Teixeira MM; 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. mmtex@icb.ufmg.br.
Jazyk: angličtina
Zdroj: Inflammation research : official journal of the European Histamine Research Society ... [et al.] [Inflamm Res] 2024 Nov; Vol. 73 (11), pp. 1903-1918. Date of Electronic Publication: 2024 Aug 30.
DOI: 10.1007/s00011-024-01939-9
Abstrakt: 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 LXA 4  (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 A 4  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.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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