Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection

Cells. 2022 Aug 31;11(17):2717. doi: 10.3390/cells11172717.

Abstract

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.

Keywords: Ac2–26 peptide; Annexin-A1; CHIKV; FPR2; neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Annexin A1 / genetics
  • Annexin A1 / metabolism
  • Arthralgia
  • Chikungunya Fever* / metabolism
  • Inflammation* / metabolism
  • Mice
  • Mice, Knockout
  • Receptors, Formyl Peptide / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Annexin A1
  • HSH2 protein, mouse
  • Receptors, Formyl Peptide
  • formyl peptide receptor 2, mouse

Grants and funding

This work received financial support from the Fapemig Hospedeiro em Dengue Project (project SUB 1 125036-1), the Medical Research Council in the United Kingdom (Newton project MR/No17544/1), the National Institute of Science and Technology in Dengue and Host-microorganism Interaction (INCT dengue) (Grant 465425/2014-3), a program funded by The Brazilian National Science Council (CNPq, Brazil) and the Minas Gerais Foundation for Science (FAPEMIG, Brazil) (project SUB 4 25036-4). This study was financed in part by the Coordination for the Improvement of Higher Education Personnel (CAPES, Brazil) (project MCTI/CNPq/CAPES/FAPS 16/2014). The authors also thank L’Oréal-UNESCO-ABC “For Women in Science” prize granted to VVC.