Conclusions
Our data demonstrate that IFP35 promotes ferroptosis by facilitating the ubiquitination and degradation of Nrf2 to exacerbate SA infection. Targeting IFP35 may be a promising approach for treating infectious diseases caused by SA.
Methods
SA infection models were established using wild-type (WT) and IFP35 knockout (Ifp35-/-) mice or macrophages. Histological analysis was performed to assess lung injury. Quantitative real-time PCR, western blotting, flow cytometry, and confocal microscopy were performed to detect ferroptosis. Co-IP and immunofluorescence were used to elucidate the molecular regulatory mechanisms.
Results
We found that IFP35 levels increased in the macrophages and lung tissue of SA-infected mice. IFP35 deficiency protected against SA-induced lung damage in mice. Moreover, ferroptosis occurred and contributed to lung injury after SA infection, which was ameliorated by IFP35 deficiency. Mechanically, IFP35 facilitated the ubiquitination and degradation of nuclear factor E2-related factor 2 (Nrf2), aggravating SA-induced ferroptosis and lung injury. Conclusions: Our data demonstrate that IFP35 promotes ferroptosis by facilitating the ubiquitination and degradation of Nrf2 to exacerbate SA infection. Targeting IFP35 may be a promising approach for treating infectious diseases caused by SA.