Houttuynia cordata triggers type I interferon signaling to promote host defense against Acinetobacter baumannii infection via mTORC1 activation

Multidrug-resistant <i>Acinetobacter baumannii</i>, a prevalent opportunistic pathogen in hospitals, presents a substantial risk to immunocompromised patients, triggering life-threatening conditions including pneumonia, bacteremia, and sepsis, which can be fatal. Therefore, it is urgent to develop new therapeutic strategies to combat and eradicate multidrug-resistant <i>A. baumannii</i> infection. Our finding reveals that <i>Houttuynia cordata</i> promotes the mice treated with 5-fluorouracil (5-FU) to defend against multidrug-resistant <i>A. baumannii</i> infection via the mTORC1-IFN-I signaling pathway. Mechanistically, <i>Houttuynia cordata</i> triggers mTORC1 activation through the phosphorylation of p38 MAPK, and mTORC1 is required for the subsequent activation of IFN-I signaling pathways in response to <i>Houttuynia cordata</i> treatment. <i>In vivo</i> studies have demonstrated that <i>Houttuynia cordata</i> enhances the clearance of <i>A. baumannii</i> in mice subjected to 5-FU chemotherapy, with this effect being mediated through the mTORC1 signaling pathway. Our study provides insight into the therapeutic intervention of enhancing IFN-I signaling and boosting host defense against bacterial infections via the administration of <i>Houttuynia cordata</i>.