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16\/2014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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 (AnxA1) 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 AnxA1-FPR2\/ALX pathway during CHIKV infection. Genetic deletion of AnxA1 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 AnxA1 mimetic peptide (Ac2\u201326) 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 AnxA1-FPR2\/ALX pathway is a potential therapeutic strategy to control CHIKV-induced acute inflammation and polyarthralgia.<\/jats:p>","DOI":"10.3390\/cells11172717","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T23:53:21Z","timestamp":1661990001000},"page":"2717","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Annexin A1-FPR2\/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection"],"prefix":"10.3390","volume":"11","author":[{"given":"Simone","family":"de Ara\u00fajo","sequence":"first","affiliation":[{"name":"Graduate 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, Brazil"},{"name":"Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor R.","family":"de Melo Costa","sequence":"additional","affiliation":[{"name":"Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franciele M.","family":"Santos","sequence":"additional","affiliation":[{"name":"Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla D. 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1102-2419","authenticated-orcid":false,"given":"Maur\u00edcio Lacerda","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Department of Dermatological, Infections, and Parasitic Diseases, School of Medicine (FAMERP), S\u00e3o Jos\u00e9 do Rio Preto, S\u00e3o Paulo 15090-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4527-6065","authenticated-orcid":false,"given":"Michelle A.","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London E1 4NS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio S.","family":"Bonilha","sequence":"additional","affiliation":[{"name":"Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"},{"name":"Center for Research on Inflammatory Diseases, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-3331","authenticated-orcid":false,"given":"Mauro","family":"Perretti","sequence":"additional","affiliation":[{"name":"Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London E1 4NS, UK"},{"name":"Centre for Inflammation and Therapeutic Innovation, Queen Mary University of London, London E1 4NS, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7478-5934","authenticated-orcid":false,"given":"Danielle G.","family":"Souza","sequence":"additional","affiliation":[{"name":"Graduate Program in 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Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5903","DOI":"10.4049\/jimmunol.0904181","article-title":"Active infection of human blood monocytes by Chikungunya virus triggers an innate immune response","volume":"184","author":"Her","year":"2010","journal-title":"J. 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