The mechanism of lentinan in preventing and treating acinetobacter baumannii pneumonia via immunomodulation

BackgroundAcinetobacter baumannii pneumonia (ABP) presents a clinical challenge due to drug resistance and immune evasion. The specific mechanism by which the natural immunomodulator lentinan (LNT) exerts anti-infective effects remains unclear. This study aimed to investigate whether LNT functions through the PINK1/Parkin-mediated mitophagy pathway.MethodsAn immunosuppressed mouse model of ABP was established, and the mice were treated with LNT alone or in combination with the mitophagy inhibitor mdivi-1. Therapeutic efficacy was evaluated through survival analysis. The bacterial load in lung tissue was determined using the plate counting method, and lung histopathology was analyzed via H&E staining. Flow cytometry was used to analyze the recruitment of immune cells (neutrophils, macrophages, dendritic cells) in bronchoalveolar lavage fluid (BALF). Inflammatory cytokine (TNF-α, IL-6, IL-1β) levels and myeloperoxidase (MPO) activity were measured using assay kits. The expression of key mitophagy-related proteins (PINK1, Parkin, Beclin-1, LC3, p62) in lung tissue was assessed by Western blot.ResultsLNT treatment significantly improved the survival rate of ABP mice, reduced bacterial load in lung tissue, and alleviated inflammatory pathological damage. LNT promoted the recruitment of neutrophils, macrophages, and dendritic cells to infection sites, while downregulating the expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β. Mechanistic studies revealed that LNT upregulated the expression of PINK1, Parkin, and Beclin-1 proteins, increased the LC3-II/I ratio, and reduced p62 accumulation. These protective effects were reversed by mdivi-1 treatment.ConclusionLNT exerts a protective effect in ABP by activating the PINK1/Parkin-mediated mitophagy pathway, thereby promoting effective immune cell recruitment and regulating inflammatory responses. This study provides a new theoretical basis for the clinical treatment of drug-resistant bacterial infections.