Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection
Chikungunya (CHIKV) is an arthritogenic alphavirus that causes a self-limiting disease usually accompanied by joint pain and/or polyarthralgia with disabling characteristics. Immune responses developed during the acute phase of CHIKV infection determine the rate of disease progression and resolution...
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MDPI AG
2022-08-01
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| author | Simone de Araújo Victor R. de Melo Costa Franciele M. Santos Carla D. Ferreira de Sousa Thaiane P. Moreira Matheus R. Gonçalves Franciel B. Félix Celso M. Queiroz-Junior Gabriel H. Campolina-Silva Maurício Lacerda Nogueira Michelle A. Sugimoto Caio S. Bonilha Mauro Perretti Danielle G. Souza Vivian V. Costa Mauro M. Teixeira |
| author_facet | Simone de Araújo Victor R. de Melo Costa Franciele M. Santos Carla D. Ferreira de Sousa Thaiane P. Moreira Matheus R. Gonçalves Franciel B. Félix Celso M. Queiroz-Junior Gabriel H. Campolina-Silva Maurício Lacerda Nogueira Michelle A. Sugimoto Caio S. Bonilha Mauro Perretti Danielle G. Souza Vivian V. Costa Mauro M. Teixeira |
| author_sort | Simone de Araújo |
| collection | DOAJ |
| description | Chikungunya (CHIKV) is an arthritogenic alphavirus that causes a self-limiting disease usually accompanied by joint pain and/or polyarthralgia with disabling characteristics. Immune responses developed during the acute phase of CHIKV infection determine the rate of disease progression and resolution. Annexin A1 (<i>AnxA1</i>) is involved in both initiating inflammation and preventing over-response, being essential for a balanced end of inflammation. In this study, we investigated the role of the <i>AnxA1-FPR2/ALX</i> pathway during CHIKV infection. Genetic deletion of <i>AnxA1</i> or its receptor enhanced inflammatory responses driven by CHIKV. These knockout mice showed increased neutrophil accumulation and augmented tissue damage at the site of infection compared with control mice. Conversely, treatment of wild-type animals with the <i>AnxA1</i> mimetic peptide (Ac<sub>2–26</sub>) reduced neutrophil accumulation, decreased local concentration of inflammatory mediators and diminished mechanical hypernociception and paw edema induced by CHIKV-infection. Alterations in viral load were mild both in genetic deletion or with treatment. Combined, our data suggest that the <i>AnxA1-FPR2/ALX</i> pathway is a potential therapeutic strategy to control CHIKV-induced acute inflammation and polyarthralgia. |
| first_indexed | 2024-03-10T01:57:17Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T01:57:17Z |
| publishDate | 2022-08-01 |
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| spelling | doaj.art-d66224f1d2c944f59ee75dc39283206a2023-11-23T12:55:47ZengMDPI AGCells2073-44092022-08-011117271710.3390/cells11172717Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus InfectionSimone de Araújo0Victor R. de Melo Costa1Franciele M. Santos2Carla D. Ferreira de Sousa3Thaiane P. Moreira4Matheus R. Gonçalves5Franciel B. Félix6Celso M. Queiroz-Junior7Gabriel H. Campolina-Silva8Maurício Lacerda Nogueira9Michelle A. Sugimoto10Caio S. Bonilha11Mauro Perretti12Danielle G. Souza13Vivian V. Costa14Mauro M. Teixeira15Graduate Program in Biological Sciences Physiology and Pharmacology, Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilDrug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilDrug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilDrug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilDrug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilDrug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilDrug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilDrug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilDrug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilDepartment of Dermatological, Infections, and Parasitic Diseases, School of Medicine (FAMERP), São José do Rio Preto, São Paulo 15090-000, BrazilBarts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London E1 4NS, UKDrug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilBarts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London E1 4NS, UKGraduate Program in Microbiology, Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilDrug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilDrug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, BrazilChikungunya (CHIKV) is an arthritogenic alphavirus that causes a self-limiting disease usually accompanied by joint pain and/or polyarthralgia with disabling characteristics. Immune responses developed during the acute phase of CHIKV infection determine the rate of disease progression and resolution. Annexin A1 (<i>AnxA1</i>) is involved in both initiating inflammation and preventing over-response, being essential for a balanced end of inflammation. In this study, we investigated the role of the <i>AnxA1-FPR2/ALX</i> pathway during CHIKV infection. Genetic deletion of <i>AnxA1</i> or its receptor enhanced inflammatory responses driven by CHIKV. These knockout mice showed increased neutrophil accumulation and augmented tissue damage at the site of infection compared with control mice. Conversely, treatment of wild-type animals with the <i>AnxA1</i> mimetic peptide (Ac<sub>2–26</sub>) reduced neutrophil accumulation, decreased local concentration of inflammatory mediators and diminished mechanical hypernociception and paw edema induced by CHIKV-infection. Alterations in viral load were mild both in genetic deletion or with treatment. Combined, our data suggest that the <i>AnxA1-FPR2/ALX</i> pathway is a potential therapeutic strategy to control CHIKV-induced acute inflammation and polyarthralgia.https://www.mdpi.com/2073-4409/11/17/2717CHIKVAnnexin-A1<i>FPR2</i>neutrophilsAc<sub>2–26</sub> peptide |
| spellingShingle | Simone de Araújo Victor R. de Melo Costa Franciele M. Santos Carla D. Ferreira de Sousa Thaiane P. Moreira Matheus R. Gonçalves Franciel B. Félix Celso M. Queiroz-Junior Gabriel H. Campolina-Silva Maurício Lacerda Nogueira Michelle A. Sugimoto Caio S. Bonilha Mauro Perretti Danielle G. Souza Vivian V. Costa Mauro M. Teixeira Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection Cells CHIKV Annexin-A1 <i>FPR2</i> neutrophils Ac<sub>2–26</sub> peptide |
| title | Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection |
| title_full | Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection |
| title_fullStr | Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection |
| title_full_unstemmed | Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection |
| title_short | Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection |
| title_sort | annexin a1 fpr2 alx signaling axis regulates acute inflammation during chikungunya virus infection |
| topic | CHIKV Annexin-A1 <i>FPR2</i> neutrophils Ac<sub>2–26</sub> peptide |
| url | https://www.mdpi.com/2073-4409/11/17/2717 |
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