Activating Dectin-1/SOCS1 signaling attenuates pseudomonas aeruginosa-induced lung injury

To investigate the role of Dectin-1 in alleviating Pseudomonas aeruginosa (PA)-induced lung injury and its underlying mechanism.

Wild-type and Dectin-1 knockout (KO) C57BL/6 mice were exposed to PAvia intratracheal instillation. PAO1 strains were cultured, inactivated, and quantified. MHS cells were used in vitro. Curdlan was employed to activate Dectin-1 signaling, and SOCS1 expression was modulated through genetic manipulation. Levels of Dectin-1, Syk, p-Syk, SOCS1, p-p65, and p65 were assessed. Lung injury was evaluated using H&E and TUNEL staining, cell counts and protein content in bronchoalveolar lavage fluid (BALF), the lung tissue wet/dry ratio, and seven-day survival rates. Bacterial burden in the lung was assessed by PA colony formation. Inflammatory responses were measured by TNF-α, IL-6, and IL-1β levels in BALF, as well as the p-p65/p65 ratio in lung or cell lysates. Apoptosis rates in cells were determined by flow cytometry.

Dectin-1 expression was downregulated in the lungs and MHS cells following PA infection. Dectin-1 depletion exacerbated PA-induced lung injury. Activation of Dectin-1 by curdlan significantly alleviated PA-induced lung injury. PA infection reduced SOCS1 expression, and SOCS1 interference exacerbated the inflammatory response and apoptosis in MHS cells, nullifying the protective effects of curdlan. Overexpression of SOCS1 significantly reduced inflammation and apoptosis in both MHS cells and Dectin-1 KO mice.

Activation of Dectin-1 significantly mitigates PA-induced lung injury, with SOCS1 playing a critical role in this process.