The annexin A1/FPR2 signaling axis expands alveolar macrophages, limits viral replication, and attenuates pathogenesis in the murine influenza A virus infection model.

摘要: Pattern recognition receptors (PRRs) are key elements in the innate immune response. Formyl peptide receptor (FPR) 2 is a PRR that, addition to proinflammatory, pathogen-derived compounds, also recognizes anti-inflammatory endogenous ligand annexin A1 (AnxA1). Because contribution of this signaling axis viral infections undefined, we investigated AnxA1-mediated FPR2 activation on influenza A virus (IAV) infection murine model. AnxA1-treated mice displayed significantly attenuated pathology upon subsequent IAV with improved survival, impaired replication respiratory tract, and less severe lung damage. The protection against was not caused by priming type I IFN response but associated an increase number alveolar macrophages (AMs) enhanced pulmonary expression AM-regulating cytokine granulocyte-M-CSF (GM-CSF). Both AM levels GM-CSF production were abrogated when mouse (m)FPR2 antagonized remained up-regulated genetically deleted for mFPR1, mFPR2 isoform serving as AnxA1 receptor. Our results indicate novel protective function AnxA1-FPR2 via GM-CSF-associated maintenance AMs, expanding knowledge potential use proresolving mediators host defense pathogens.-Schloer, S., Hubel, N., Masemann, D., Pajonczyk, Brunotte, L., Ehrhardt, C., Brandenburg, L.-O., Ludwig, Gerke, V., Rescher, U. A1/FPR2 expands macrophages, limits replication, attenuates pathogenesis