Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease
Host immune responses contribute to dengue’s pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant infl...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/73853 |
| _version_ | 1811235808379666432 |
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| author | Vivian Vasconcelos Costa Michelle A Sugimoto Josy Hubner Caio S Bonilha Celso Martins Queiroz-Junior Marcela Helena Gonçalves-Pereira Jianmin Chen Thomas Gobbetti Gisele Olinto Libanio Rodrigues Jordana L Bambirra Ingredy B Passos Carla Elizabeth Machado Lopes Thaiane P Moreira Kennedy Bonjour Rossana CN Melo Milton AP Oliveira Marcus Vinicius M Andrade Lirlândia Pires Sousa Danielle Gloria Souza Helton da Costa Santiago Mauro Perretti Mauro Martins Teixeira |
| author_facet | Vivian Vasconcelos Costa Michelle A Sugimoto Josy Hubner Caio S Bonilha Celso Martins Queiroz-Junior Marcela Helena Gonçalves-Pereira Jianmin Chen Thomas Gobbetti Gisele Olinto Libanio Rodrigues Jordana L Bambirra Ingredy B Passos Carla Elizabeth Machado Lopes Thaiane P Moreira Kennedy Bonjour Rossana CN Melo Milton AP Oliveira Marcus Vinicius M Andrade Lirlândia Pires Sousa Danielle Gloria Souza Helton da Costa Santiago Mauro Perretti Mauro Martins Teixeira |
| author_sort | Vivian Vasconcelos Costa |
| collection | DOAJ |
| description | Host immune responses contribute to dengue’s pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, interferon (alpha and beta) receptor one knockout (KO), AnxA1 KO, and formyl peptide receptor 2 (FPR2) KO mice were infected with dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac2-26 for analysis. In addition, the effect of Ac2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. Whilst the absence of AnxA1 or its receptor FPR2 aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestationsatteanuated the symptoms of the disease. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease. |
| first_indexed | 2024-04-12T11:58:25Z |
| format | Article |
| id | doaj.art-978130634ef5433b81f6a6ec6017ebd3 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T11:58:25Z |
| publishDate | 2022-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-978130634ef5433b81f6a6ec6017ebd32022-12-22T03:33:56ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.73853Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue diseaseVivian Vasconcelos Costa0https://orcid.org/0000-0002-0175-642XMichelle A Sugimoto1https://orcid.org/0000-0002-4527-6065Josy Hubner2Caio S Bonilha3Celso Martins Queiroz-Junior4Marcela Helena Gonçalves-Pereira5Jianmin Chen6Thomas Gobbetti7Gisele Olinto Libanio Rodrigues8Jordana L Bambirra9Ingredy B Passos10Carla Elizabeth Machado Lopes11Thaiane P Moreira12Kennedy Bonjour13Rossana CN Melo14Milton AP Oliveira15Marcus Vinicius M Andrade16Lirlândia Pires Sousa17https://orcid.org/0000-0002-1042-9762Danielle Gloria Souza18Helton da Costa Santiago19Mauro Perretti20https://orcid.org/0000-0003-2068-3331Mauro Martins Teixeira21https://orcid.org/0000-0002-6944-3008Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United KingdomDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United KingdomDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartment of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartment of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartment of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartment of Biology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, BrazilDepartment of Biology, Institute of Biological Sciences, Federal University of Juiz de Fora, Juiz de Fora, BrazilTropical Pathology and Public Health Institute, Universidade Federal de Goiás, Goiânia, BrazilSchool of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartment of Clinical and Toxicological Analyses, School of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartment of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom; Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London, United KingdomDepartment of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilHost immune responses contribute to dengue’s pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, interferon (alpha and beta) receptor one knockout (KO), AnxA1 KO, and formyl peptide receptor 2 (FPR2) KO mice were infected with dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac2-26 for analysis. In addition, the effect of Ac2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. Whilst the absence of AnxA1 or its receptor FPR2 aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestationsatteanuated the symptoms of the disease. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease.https://elifesciences.org/articles/73853dengue diseaseAnnexin A1 pro-resolving proteinFPR2/ALX receptorinflammation resolutionAc2-26 pro-resolving peptidedengue virus |
| spellingShingle | Vivian Vasconcelos Costa Michelle A Sugimoto Josy Hubner Caio S Bonilha Celso Martins Queiroz-Junior Marcela Helena Gonçalves-Pereira Jianmin Chen Thomas Gobbetti Gisele Olinto Libanio Rodrigues Jordana L Bambirra Ingredy B Passos Carla Elizabeth Machado Lopes Thaiane P Moreira Kennedy Bonjour Rossana CN Melo Milton AP Oliveira Marcus Vinicius M Andrade Lirlândia Pires Sousa Danielle Gloria Souza Helton da Costa Santiago Mauro Perretti Mauro Martins Teixeira Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease eLife dengue disease Annexin A1 pro-resolving protein FPR2/ALX receptor inflammation resolution Ac2-26 pro-resolving peptide dengue virus |
| title | Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease |
| title_full | Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease |
| title_fullStr | Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease |
| title_full_unstemmed | Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease |
| title_short | Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease |
| title_sort | targeting the annexin a1 fpr2 alx pathway for host directed therapy in dengue disease |
| topic | dengue disease Annexin A1 pro-resolving protein FPR2/ALX receptor inflammation resolution Ac2-26 pro-resolving peptide dengue virus |
| url | https://elifesciences.org/articles/73853 |
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