Lipopolysaccharide priming confers trained immunity and enhances antiviral defense against Sendai virus via STAT1/2 signaling

Abstract

Trained immunity, the functional reprogramming of innate immune cells that enhances responses to secondary challenges, represents a paradigm shift in our understanding of immune memory. We investigated whether lipopolysaccharide (LPS) priming could induce trained immunity against respiratory viral infection. C57BL/6 N mice pre-treated with LPS exhibited significant protection against Sendai virus challenge, with reduced disease severity and viral titers. This protective effect was mediated by functional reprogramming of multiple innate immune cell types, including alveolar macrophages, mononuclear cells, and polymorphonuclear cells. Mechanistically, LPS priming established an enhanced antiviral state characterized by rapid STAT1/2 phosphorylation and interferon-stimulated gene expression upon viral encounter. The trained immune response was further characterized by balanced cytokine production (IL-1β, IL-17 A, IL-10), promoting viral clearance without excessive inflammation. Our findings demonstrate that trained immunity operates across diverse innate immune cell populations in the lung, providing a mechanistic basis for harnessing innate immune memory as a broad-spectrum antiviral strategy.