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Published on: November 17, 2023
The roles of tissue-resident macrophages in sepsis-associated organ dysfunction
Yulei Gao1,2, Xin Tian3,4, Xiang Zhang5
1Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, P. R. China.
Abstract:
Sepsis, a syndrome caused by a dysregulated host response to infection and characterized by life-threatening organ dysfunction, particularly septic shock and sepsis-associated organ dysfunction (SAOD), is a medical emergency associated with high morbidity, high mortality, and long-term sequelae. Tissue-resident macrophages (TRMs) are a subpopulation of macrophages derived primarily from yolk sac progenitors and fetal liver during embryogenesis, located primarily in non-lymphoid tissues in adulthood, capable of local self-renewal independent of hematopoiesis, and developmentally and functionally restricted to the non-lymphoid organs in which they reside. TRMs are the first line of defense against life-threatening conditions such as sepsis, tumor growth, traumatic-associated organ injury, and surgical-associated injury. In the context of sepsis, TRMs can be considered as angels or demons involved in organ injury. Our proposal is that sepsis, septic shock, and SAOD can be attenuated by modulating TRMs in different organs. This review summarizes the pathophysiological mechanisms of TRMs in different organs or tissues involved in the development and progression of sepsis.
Insights
Tissue-resident macrophages (TRMs) play a dual role in sepsis, acting as both protectors and contributors to organ injury. Modulating TRMs offers a promising therapeutic strategy to mitigate sepsis, septic shock, and sepsis-associated organ dysfunction (SAOD).
Area of Science:
- Immunology
- Pathophysiology
- Cell Biology
Background:
- Sepsis is a life-threatening condition characterized by organ dysfunction due to a dysregulated host response to infection.
- Tissue-resident macrophages (TRMs) are critical immune cells residing in non-lymphoid tissues, originating from early embryonic progenitors.
- TRMs are essential for local tissue homeostasis and defense against various insults, including infection.
Purpose of the Study:
- To review the pathophysiological roles of TRMs in the development and progression of sepsis.
- To explore the dual "angel" and "demon" functions of TRMs in sepsis-induced organ injury.
- To propose TRM modulation as a potential therapeutic strategy for sepsis, septic shock, and SAOD.
Main Methods:
- Literature review summarizing existing research on TRMs and sepsis.
- Analysis of pathophysiological mechanisms linking TRMs to organ dysfunction in sepsis.
- Synthesis of evidence supporting TRM modulation for sepsis treatment.
Main Results:
- TRMs exhibit context-dependent roles in sepsis, contributing to both protective immunity and detrimental inflammation.
- TRM function and phenotype vary across different organs during sepsis.
- Dysregulated TRM activity is implicated in sepsis-associated organ dysfunction (SAOD) and septic shock.
Conclusions:
- TRMs are key players in sepsis pathogenesis, influencing disease severity and outcomes.
- Targeting TRMs in various organs presents a novel therapeutic avenue for managing sepsis and its complications.
- Further research into TRM-specific mechanisms is crucial for developing effective immunomodulatory therapies.
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