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
Victor R. de Melo Costa
Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
Franciele M. Santos
Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
Carla D. Ferreira de Sousa
Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
Thaiane P. Moreira
Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
Matheus R. Gonçalves
Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
Franciel B. Félix
Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
Celso M. Queiroz-Junior
Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
Gabriel H. Campolina-Silva
Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
Maurício Lacerda Nogueira
Department of Dermatological, Infections, and Parasitic Diseases, School of Medicine (FAMERP), São José do Rio Preto, São Paulo 15090-000, Brazil
Michelle A. Sugimoto
Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London E1 4NS, UK
Caio S. Bonilha
Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
Mauro Perretti
Barts and The London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London E1 4NS, UK
Danielle G. Souza
Graduate Program in Microbiology, Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
Vivian V. Costa
Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
Mauro M. Teixeira
Drug Research and Development Center, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil
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 (Ac2–26) 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.
