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The Annexin A1/FPR2 pathway controls the inflammatory response and bacterial dissemination in experimental pneumococcal pneumonia
Author(s) -
Machado Marina Gomes,
Tavares Luciana Pádua,
Souza Geovanna V. Santos,
QueirozJunior Celso M.,
Ascenção Fernando Roque,
Lopes Mateus Eustáquio,
Garcia Cristiana Couto,
Menezes Gustavo Batista,
Perretti Mauro,
Russo Remo Castro,
Teixeira Mauro Martins,
Sousa Lirlândia Pires
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902172r
Subject(s) - annexin a1 , inflammation , streptococcus pneumoniae , pneumonia , pneumococcal pneumonia , bacterial pneumonia , immunology , phagocytosis , lung , microbiology and biotechnology , medicine , biology , annexin , antibiotics , flow cytometry
Abstract Streptococcus pneumoniae is a major cause of community‐acquired pneumonia leading to high mortality rates. Inflammation triggered by pneumococcal infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Annexin A1 (AnxA1) mainly acts through Formyl Peptide Receptor 2 (FPR2) inducing the resolution of inflammation. Here, we have evaluated the role of AnxA1 and FPR2 during pneumococcal pneumonia in mice. For that, AnxA1, Fpr2/3 knockout (KO) mice and wild‐type (WT) controls were infected intranasally with S pneumonia e. AnxA1 and Fpr2/3 KO mice were highly susceptible to infection, displaying uncontrolled inflammation, increased bacterial dissemination, and pulmonary dysfunction compared to WT animals. Mechanistically, the absence of AnxA1 resulted in the loss of lung barrier integrity and increased neutrophil activation upon S pneumoniae stimulation. Importantly, treatment of WT or AnxA1 KO‐infected mice with Ac2‐26 decreased inflammation, lung damage, and bacterial burden in the airways by increasing macrophage phagocytosis. Conversely, Ac2‐26 peptide was ineffective to afford protection in Fpr2/3 KO mice during infection. Altogether, these findings show that AnxA1, via FPR2, controls inflammation and bacterial dissemination during pneumococcal pneumonia by promoting host defenses, suggesting AnxA1‐based peptides as a novel therapeutic strategy to control pneumococcal pneumonia.