Quercitrin Inhibits NETosis via Histone H3 to Alleviate the Severity of Viral Pneumonia With Drug‐Resistant Bacteria Co‐Infection in Mice

ABSTRACT Secondary bacterial infection is a major cause of severe progression and death in viral pneumonia. The excessive recruitment of neutrophils accompanied by the formation of neutrophil extracellular traps (NETs) plays an important role in excessive inflammation caused by viral‐bacterial co‐infection, but effective pharmacological interventions remain lacking. Our study revealed that quercitrin (QTN), a flavonoid commonly found in traditional Chinese medicine and daily diets, significantly reduced mortality, recruitment of neutrophils, the production of inflammatory cytokines, and viral and bacterial loads in H1N1 influenza and methicillin‐resistant Staphylococcus aureus (MRSA) coinfection‐induced pneumonia in mice. Mechanistically, QTN down‐regulates the interaction between Histone H3 and myeloperoxidase (MPO), thereby mitigating excessive inflammation induced by NETs. Our study demonstrates that inhibiting NETosis with QTN is one of the effective strategies for co‐infection treatment.