Immunological features of sepsis phenotypes and endotypes

Sepsis is a heterogeneous and life-threatening condition caused by a dysregulated immune response to infection. The most severe form of sepsis is septic shock, characterized by arterial hypotension, impaired tissue perfusion, and hypoxia. Despite new findings in antimicrobial and intensive care therapy, the incidence and mortality rates of sepsis remain high, which underscores the relevance of further studies on its pathogenesis. In recent years, the research has shifted from clinical signs to analysis of immunological and molecular mechanisms, which allowed to identify specific phenotypes and endotypes of the disease. Sepsis phenotypes are based on clinical manifestations and biomarkers, whereas its endotypes are defined by molecular mechanisms, including immune gene expression patterns. This article reviews key aspects of the innate and adaptive immune responses in sepsis, including activation of proinflammatory cytokines, development of coagulopathies, deterioration of endothelial integrity and microvascular regulation. Moreover, the potential mechanisms, e.g., hyperinflammation, simultaneous development of immunosuppression, and functional exhaustion of immunocompetent cells are highlighted. Thus, immunological biomarkers are considered a promising tool for patient‘s stratification, prognosis prediction and personalized therapy. Current immunodiagnostic methods are also discussed in this article, including quantitative analysis of cytokine levels and assessment of innate immune dysfunction markers. Hence, current understanding of sepsis as an immunologically heterogeneous syndrome enables researchers to expand existing concepts of its pathogenesis. In contrast to classical concept based on a shift from inflammation to immune suppression, the novel results suggest a simultaneous presence of both processes in the same patient, making it necessary to reconsider the existing diagnostic and therapeutic approaches.