The EVs containing histones released by mouse-derived BMDM interact with TLR4, displaying pro-inflammatory effect, which can promote the production of TNF, IL-6 and IL-1β, thereby increasing the lethality of sepsis (Xu et al., 2009; Nair et al., 2018; Burgelman et al., 2021; Li Y. et al., 2021). Here, TNF is linked to Sepsis.