Extracellular HSP70 facilitated β-glucan induced trained immunity in macrophages to suppress sepsis via TLR2-NF-κB axis.

Sepsis is a common systemic infectious disease followed by extremely high incidence and mortality with no effective treatment and clinical drugs. As a key mediator involved in infection and immunity, it has been reported that sepsis patients are accompanied by increased heat shock protein 70 (HSP70). Trained immunity is a novel innate immunity approach that can be activated by β-glucan to fight against sepsis. The mechanism of HSP70 activating trained macrophages against sepsis needs further elucidation. Trained immunity and sepsis models were established by β-glucan and LPS individually both in vivo and in vitro. We demonstrated that HSP70 was significantly upregulated in septic mice serum, and HSP70 could protect mice from sepsis by activating β-glucan-trained macrophages as an ideal secondary inducer via TLR2-NF-κB pathway. Additionally, the sepsis resistant effects of HSP70 could be blocked by its antibody. In summary, more than a molecular chaperone to maintain homeostasis, HSP70 could be an important trained immunity inducer to help the body fighting against sepsis, which provided new stimuli for trained immunity and novel therapeutic solutions for sepsis.