Hexa-acylated LPS-lipid A deploys the appropriate level of fibrin to confer protection through MyD88.

•Fibrin has been demonstrated to function protectively against pathogens in previous studies, but a very high level of fibrin played a negative role during some infections.•An appropriate fibrin level performs critical protective roles during defense against plague, revealing the “double-edged sword” characteristic of fibrin during infections.•We demonstrated that the appropriate level of fibrin formation was deployed by hexa-acylated LPS-lipid A through myeloid differentiation factor 88.