Sepsis: Heterogeneity, Immunopathology, and Advances in Therapeutic Strategies

Sepsis is a heterogeneous syndrome characterized by a dysregulated host response to infection resulting in life-threatening organ dysfunction. It has emerged as one of the most critical causes of mortality worldwide, imposing not only substantial physical and economic burdens on patients and their families but also creating a significant strain on healthcare systems worldwide. Despite its severity, the absence of targeted effective therapeutics remains a disappointing and persistent challenge in clinical management. This underscores the urgent need to develop a more comprehensive understanding of sepsis and to elucidate its underlying pathophysiological mechanisms, which is essential for identifying novel therapeutic strategies. In this review, we synthesize recent advances in sepsis subphenotypes, diagnostic criteria, and associated complications, with particular emphasis on alterations in the host immune response. This includes an analysis of the functional states of key immune cells and the dynamic interplay between the host and gut microbiota. Furthermore, we discuss future directions and potential innovative treatments for sepsis. It is anticipated that this comprehensive overview may provide new perspectives and avenues for improving the prognosis and management of sepsis.