IFNA1 and infection: In this first dedicated study on the impact of itaconate and derivatives on host responses to IAV infection, we found that (i) the endogenous ACOD1/itaconate axis limits pulmonary inflammation due to the infection in a murine model, (ii) ectopically expressed ACOD1 possesses anti-IFN activity in an epithelial cell line that normally does not express this enzyme, and (iii) that exogenously applied itaconate and/or derivatives restrict IFN-responses and modulate classic pro-inflammatory cytokines across all models tested, whereas antiviral effects were most strongly associated with 4OI.