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Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation
Emilia Nunzi1, Letizia Mezzasoma1, Ilaria Bellezza1
1Department of Medicine and Surgery, University of Perugia, Polo Unico Sant'Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, Italy.
International Journal of Molecular Sciences
|February 11, 2023
Summary
Human amniotic fluid extracellular vesicles (HAF-EVs) modulate monocyte inflammasome activation, potentially balancing immune tolerance during pregnancy. These vesicles may harbor specific early pregnancy microbiota.
Area of Science:
- Immunology
- Cell Biology
- Pregnancy Research
Background:
- Human amniotic fluid extracellular vesicles (HAF-EVs) possess immunoregulatory functions in pregnancy.
- The precise mechanisms by which HAF-EVs influence immune cells, particularly monocytes, remain incompletely understood.
- Investigating HAF-EVs' impact on inflammasome activation is crucial for understanding their role in immune modulation.
Purpose of the Study:
- To investigate the effect of HAF-EVs on inflammasome activation in human monocytes.
- To identify potential sources of endotoxin associated with HAF-EVs.
- To explore the immunoregulatory potential of HAF-EVs in balancing immune training and tolerance.
Main Methods:
- Isolation and purification of HAF-EVs from amniotic fluid via gradient ultracentrifugation.
- Proteomic and metagenomic analyses of HAF-EVs to identify molecular components and associated microbiota.
- Treatment of THP-1 cells (monocyte cell line) with HAF-EVs, followed by stimulation with LPS and ATP to assess inflammasome activation.
- Bioinformatics analysis of microbiota-HAF-EVs functional pathways.
Main Results:
- HAF-EVs expressed immunoregulatory molecules and contained small amounts of endotoxin.
- Metagenomic analysis revealed bacterial strain variants associated with HAF-EVs as potential endotoxin sources.
- HAF-EVs alone triggered inflammasome activation in THP-1 cells, while prior HAF-EV treatment prevented subsequent LPS/ATP-induced activation, mimicking monocyte refractoriness.
- Bioinformatics confirmed enzymes for endotoxin biosynthesis and immunoregulatory functions within microbiota-HAF-EVs pathways.
Conclusions:
- HAF-EVs may serve as a source for isolating specific early pregnancy microbiota.
- HAF-EVs can modulate monocyte inflammasome activation, suggesting a role in immune training and tolerance.
- These findings highlight HAF-EVs as a novel system for immune system regulation during pregnancy.
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