Sepsis roadmap: What we know, what we learned, and where we are going.

Sepsis is a life-threatening condition originating as a result of systemic blood infection causing, one or more organ damage due to the dysregulation of the immune response. In 2017, the world health organization (WHO) declared sepsis as a disease of global health priority, needing special attention due to its high prevalence and mortality around the world. Most of the therapeutics targeting sepsis have failed in the clinics. The present review highlights the history of the sepsis, its immunopathogenesis, and lessons learned after the failure of previously used immune-based therapies. The subsequent section, where to go describes in details the importance of the complement system (CS), autophagy, inflammasomes, and microbiota along with their targeting to manage sepsis. These systems are interconnected to each other, thus targeting one may affect the other. We are in an urgent need for a multi-targeting therapeutic approach for sepsis.