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Review
. 2025 Jan 24;29(1):43.
doi: 10.1186/s13054-025-05278-x.

The role of programmed cell death in organ dysfunction induced by opportunistic pathogens

Yangyanqiu Wang  1 , Li Weng  1 , Xunyao Wu #  2 , Bin Du #  3   4
Affiliations
Review

The role of programmed cell death in organ dysfunction induced by opportunistic pathogens

Yangyanqiu Wang et al. Crit Care. .

Abstract

Sepsis is a life-threatening condition resulting from pathogen infection and characterized by organ dysfunction. Programmed cell death (PCD) during sepsis has been associated with the development of multiple organ dysfunction syndrome (MODS), impacting various physiological systems including respiratory, cardiovascular, renal, neurological, hematological, hepatic, and intestinal systems. It is well-established that pathogen infections lead to immune dysregulation, which subsequently contributes to MODS in sepsis. However, recent evidence suggests that sepsis-related opportunistic pathogens can directly induce organ failure by promoting PCD in parenchymal cells of each affected organ. This study provides an overview of PCD in damaged organ and the induction of PCD in host parenchymal cells by opportunistic pathogens, proposing innovative strategies for preventing organ failure in sepsis.

Keywords: Opportunistic pathogens; Organ failure; Programmed cell death; Sepsis.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
In sepsis, cell death mechanisms such as apoptosis, necroptosis, pyroptosis, autophagy and ferroptosis play a direct role in organ dysfunction. Apoptosis and autophagy typically help to remove damaged cells and prevent the spread of inflammation. However, during sepsis, excessive apoptosis and damaged autophagy can result in the loss of many functional and unable to remove damaged cells, thereby weakening organ function. Necroptosis, pyroptosis and ferroptosis may dysregulate inflammatory factors, exacerbating the inflammatory response and causing further tissue and organ damage. Thus, the imbalance of cell death pathways is a critical pathological basis for organ dysfunction in sepsis. The major organ systems that are clinically monitored in patients with sepsis was adapted from Lelubre and Vincent 14]
Fig. 2
Fig. 2
Opportunistic pathogenic bacteria elicit the death of organ parenchymal cells by triggering and fine-tuning cell death mechanisms such as apoptosis, necrosis, pyroptosis, autophagy, and ferroptosis, with key molecule interactions in these programmed cell death pathways depicted; this cell death is a critical driver of severe organ dysfunction and the pathological course of sepsis
Fig. 3
Fig. 3
Pathogenic viruses exploit various cell death mechanisms, including apoptosis, necrosis, pyroptosis, autophagy, and ferroptosis, to induce the demise of organ parenchymal cells, as illustrated by the key molecular interactions within these pathways; this process is a major contributor to the development of severe organ impairment and the progression of sepsis
See this image and copyright information in PMC

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