Unraveling the role of exosomes in intercellular crosstalk and organ dysfunction

Sepsis, a life-threatening systemic response to infection, continues to pose significant challenges in healthcare, causing substantial morbidity and mortality worldwide. In recent years, emerging research has shed light on the role of exosomes, tiny vesicles involved in cell-to-cell communication, in the complex pathogenesis of sepsis.

Researchers at the University of Pittsburgh School of Medicine discuss exosomes and their pivotal role in orchestrating various aspects of the septic response. They begin by exploring the basics of exosome biogenesis and characterization, providing a foundational understanding of their diverse functions.

Mechanisms of exosome regulation of immunity in sepsis

Fig. 1

Exosomes derived from immune cells are instrumental in orchestrating a balance between immunoregulatory and autoimmune responses within a complex network of immune interactions. These vesicles are rich in bioactive molecules and play key roles in the inflammatory process by guiding PMN recruitment and migration, supporting the innate immune response, and influencing macrophage polarization towards either pro-inflammatory M1 or anti-inflammatory M2 states, thereby shaping the progression of inflammation. DC-derived exosomes are crucial in engaging memory T cells, triggering their differentiation into Th1, Th2, or Treg cells and fostering a proliferative response essential for robust immunity. Additionally, these exosomes enhance adaptive immunity by aiding in B cell maturation and improving antigen presentation. Simultaneously, they significantly impact the activation and proliferation of CD8+ T cells, highlighting their extensive involvement in modulating immune responses, particularly during sepsis. PMN neutrophil, DC dendritic cell, NET neutrophil extracellular traps, Th1 type 1 helper T cells, Th2 type 2 helper T cells, Ab antibody

Moving forward, they dissect the regulatory roles of exosomes in key immune cells, including neutrophils, macrophages, dendritic cells, T cells, and B cells. These tiny vesicles wield significant influence over immune responses, shaping the landscape of sepsis pathophysiology.

Furthermore, the researchers investigate the involvement of exosomes in metabolic reprogramming and organ dysfunction during sepsis. By delving into their impact on the coagulation cascade and endothelial integrity, they uncover the intricate connections between exosomes and thrombogenesis in sepsis.

Moreover, they explore the dual nature of exosomes in sepsis progression and resolution, highlighting their complex interplay in inflammation and healing processes.

Finally, they researchers discuss the potential of exosomes as biomarkers and therapeutic targets in sepsis management. By understanding these mechanisms, they unlock new avenues for innovative interventions aimed at mitigating the devastating consequences of sepsis, underscoring the therapeutic promise of exosome research in critical care settings.

This review underscores the pivotal role of exosomes in sepsis and emphasizes the transformative potential of exosome-based interventions in improving patient outcomes. As we continue to unravel the complexities of sepsis pathogenesis, exosome research stands at the forefront of innovation in critical care medicine.

Gong T, Liu YT, Fan J. (2024) Exosomal mediators in sepsis and inflammatory organ injury: unraveling the role of exosomes in intercellular crosstalk and organ dysfunction. Mil Med Res 11(1):24. [article]

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