Circular RNA circMagi1 regulates the host immune response in respiratory <i>Pseudomonas aeruginosa</i> infection through G3BP2

<i>Pseudomonas aeruginosa</i> is a major pathogen responsible for hospital-acquired infections, and it is characterized by possessing easy colonization ability, being difficult to clear, and exhibiting pandrug resistance. After a host is infected with pathogenic bacteria, multiple molecules regulate immune defense mechanisms through synergistic or antagonistic effects. Circular RNAs (circRNAs), characterized by their closed loop structure, are noncoding RNAs that are extensively expressed in various tissues. They have been reported to play a role in a range of physiological and pathological processes within the host. However, their involvement in regulating the immune activation mechanism against bacterial infection remains uncertain. In this study, we identified circMagi1, a circRNA that is significantly downregulated after infection in both a mouse model of lung infection and patients with lung infections. circMagi1 functions mainly as a negative regulator of immune activation for immune homeostasis. Further research has shown that it affects the cytokine signaling axis in macrophages by regulating the G3BP2 protein. Therefore, circMagi1 may function as a promising diagnostic biomarker for bacterial pathogen infections.IMPORTANCECircular RNAs (circRNAs) have been reported to be widely involved in the occurrence and development of various diseases, including cancer and neurodegenerative diseases, but there are few reports on circRNAs regulating host immune activation in bacterial infection. On the other hand, in contrast to the well-characterized progress and treatment of the disease and the prevalence of bacterial resistance in <i>Pseudomonas aeruginosa</i> pulmonary infection in recent decades, research on the mechanism of host-pathogen interactions and the regulatory mechanism of the host immune microenvironment has gained less attention. In this study, we constructed a mouse model of <i>P. aeruginosa</i> lung infection and analyzed patient alveolar lavage fluid samples, identifying a circRNA that is significantly downregulated postinfection. Our further investigation revealed that circMagi1 interacts with the G3BP2 protein, increasing its stability by inhibiting its ubiquitination. This newly discovered mechanism helps us understand how the host prevents excessive immune activation during bacterial infection.