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Mitochondrial Network Fragmentation Leads to Dysfunction of Macrophages During Echinococcus multilocularis
Zihan Yang1,2,3,4, Yaogang Zhang5,6, Tao Zhang7
1Research Center for High Altitude Medicine, Qinghai University, Xining 810000, China.
Abstract:
Alveolar echinococcosis (AE) is a fatal foodborne parasitic disease caused by the larvae of Echinococcus multilocularis. The disease primarily affects the liver. Previous studies have found that Kupffer cells have an immune protective effect, but in the late stages of AE, they are associated with parasite immune escape. The present study analyzed the effects of Echinococcus multilocularis protoscoleces (PSCs) infection on the mitochondrial morphology and function of macrophages, as well as their phagocytic function and apoptosis. Infection with PSCs has been shown to result in the fragmentation of the macrophage mitochondrial network, the impairment of mitochondrial membrane potential, the elevation of mitochondrial reactive oxygen species, and the reduction in mitochondrial DNA copy number. This cascade of events, consequent to the infection, has been demonstrated to promote the apoptosis of macrophages and impair their phagocytic function. Inhibiting mitochondrial fission during PSCs infection has been shown to mitigate mitochondrial dysfunction, suppress macrophage apoptosis, and enhance macrophage phagocytic function. This discovery provides insights into improving macrophage function during the progression of AE.
Insights
Alveolar echinococcosis (AE) infection disrupts macrophage mitochondria, impairing immune response. Targeting mitochondrial fission could improve macrophage function and combat this parasitic disease.
Area of Science:
- Immunology
- Parasitology
- Cell Biology
Background:
- Alveolar echinococcosis (AE) is a severe liver disease caused by *Echinococcus multilocularis*.
- Kupffer cells (macrophages in the liver) play a dual role in AE, offering protection but also aiding parasite immune escape in later stages.
Purpose of the Study:
- To investigate the impact of *Echinococcus multilocularis* protoscoleces (PSCs) on macrophage mitochondrial morphology and function.
- To assess the effects of PSCs infection on macrophage phagocytosis and apoptosis.
- To explore the therapeutic potential of inhibiting mitochondrial fission in AE.
Main Methods:
- Macrophages were infected with *Echinococcus multilocularis* protoscoleces (PSCs).
- Mitochondrial morphology, membrane potential, reactive oxygen species (ROS) levels, and mitochondrial DNA (mtDNA) copy number were analyzed.
- Macrophage phagocytic activity and apoptosis rates were measured.
- The effect of inhibiting mitochondrial fission was evaluated.
Main Results:
- PSCs infection led to mitochondrial network fragmentation, reduced membrane potential, increased ROS, and decreased mtDNA copy number in macrophages.
- These mitochondrial changes promoted macrophage apoptosis and impaired their phagocytic function.
- Inhibiting mitochondrial fission reversed mitochondrial dysfunction, reduced apoptosis, and enhanced phagocytosis.
Conclusions:
- *Echinococcus multilocularis* protoscoleces disrupt macrophage mitochondria, contributing to immune evasion in alveolar echinococcosis.
- Targeting mitochondrial fission presents a promising strategy to restore macrophage function and treat AE.
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