Figure 1.

Model of how FPR2 promotes harmful inflammation in a time scale manner. At early stages post-infection, Annexin A1 incorporated into IAV, activates FPR2 leading to (i) an anti-inflammatory state, which impairs host immune response and provides the mean for IAV to replicate. In addition (ii), FPR2-signaling activates the ERK pathway, further increasing IAV replication. Altogether, IAV replication fosters PRR activation, leading to a dysregulated and excessive innate immune response. During the time course of infection, infected cells undergo apoptosis, leading to the release of mitochondrial formylated peptides. In addition, proteases are released in a large amount by leucocytes that are recruited to the site of infection. Those proteases cleave Annexin A1 incorporated into IAV. FPR2, which is then activated by formylated peptides and cleaved Annexin A1 turns pro-inflammatory. This further contributes at later stages post-infection to increased inflammation and IAV pathogenesis.