IFN-γ exacerbates sepsis-driven immune suppression by modulating PMN-MDSCs

Le résumé fourni par la source

Persistent immunosuppression during sepsis poses a significant challenge to patient recovery. Moreover, the efficacy of interferon-gamma (IFN-γ) as an immunostimulatory therapy in sepsis has proven limited. In this study, using a cecal ligation and puncture (CLP)-induced mouse model of sepsis, we identified a previously unrecognized mechanism by which IFN-γ promotes both the expansion and immunosuppressive activity of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) during the immunosuppressive phase of sepsis, thereby contributing to its suboptimal therapeutic efficacy. In vitro experiments further demonstrated that IFN-γ augments PMN-MDSC function through a STAT1-dependent upregulation of PD-L1. Building on these insights, we developed a novel combination therapy incorporating IFN-γ and an anti-PD-L1 agent, which demonstrated significant efficacy in a murine model of sepsis-induced immunosuppression. In summary, our study identifies a critical drawback of IFN-γ monotherapy in sepsis and proposes a promising combined strategy to counteract sepsis-associated immunosuppression.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.