Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease

• DOI: 10.7554/elife.73853
• Publication Date: 2022-03-16T13:01:31Z
• Authors: Vivian Vasconcelo...; Michelle A Sugimoto; Josy Hubner; Caio S Bonilha; Celso Martins Que...; Marcela Helena Go...; Jianmin Chen; Thomas Gobbetti; Gisele Olinto Lib...; Jordana L Bambirra; Ingredy B Passos; Carla Elizabeth M...; Thaiane P Moreira; Kennedy Bonjour; Rossana CN Melo; Milton AP Oliveira; Marcus Vinicius M...; Lirlândia Pires S...; Danielle Gloria S...; Helton da Costa S...; Mauro Perretti; Mauro Martins Tei...
• Keywords: Annexin A1; Cytokine Storm

Host immune responses contribute to dengue’s pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known counterbalance overexuberant mast cell (MC) activation. We hypothesised inadequate AnxA1 engagement underlies cytokine storm vascular pathologies associated with dengue disease. Levels of were examined plasma patients infected mice. Immunocompetent, interferon (alpha beta) receptor one knockout (KO), KO, formyl peptide 2 (FPR2) KO mice virus (DENV) treated mimetic Ac 2-26 for analysis. In addition, effect on DENV-induced MC degranulation was assessed vitro vivo. observed circulating levels reduced DENV-infected Whilst absence or its FPR2 aggravated illness mice, treatment agonistic attenuated manifestationsatteanuated symptoms Both clinical outcomes attributed modulation DENV-mediated viral load-independent degranulation. have thereby identified altered mediator are pathological relevance DENV infection, suggesting FPR2/ALX agonists as a therapeutic target