Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation

被引：8

作者：

Nunzi, Emilia ^{[1
]}

Mezzasoma, Letizia ^{[1
]}

Bellezza, Ilaria ^{[1
]}

Zelante, Teresa ^{[1
]}

Orvietani, Pierluigi ^{[1
]}

Coata, Giuliana ^{[1
]}

Giardina, Irene ^{[2
]}

Sagini, Krizia ^{[3
]}

Manni, Giorgia ^{[1
]}

Di Michele, Alessandro ^{[4
]}

Gargaro, Marco ^{[1
]}

Talesa, Vincenzo N. ^{[1
]}

Di Renzo, Gian Carlo ^{[5
]}

Fallarino, Francesca ^{[1
]}

Romani, Rita ^{[1
]}

机构：

[1] Univ Perugia, Dept Med & Surg, Polo Un St Andrea Fratte,Pe Lucio Severi 1, I-06132 Perugia, Italy

[2] Univ Hosp Perugia, Dept Obstet & Gynecol, St Andrea Fratte,Pe Lucio Severi 1, I-06132 Perugia, Italy

[3] Norwegian Radium Hosp, Oslo Univ Hosp, Inst Canc Res, Dept Mol Cell Biol, N-0379 Oslo, Norway

[4] Univ Perugia, Dept Phys & Geol, Via Pascoli, I-06123 Perugia, Italy

[5] IM Sechenov First State Univ, Dept Obstet Gynecol & Perinatol, Moscow 117997, Russia

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 03期

基金：

英国科研创新办公室;

关键词：

extracellular vesicles; amniotic fluid; LPS; metagenomic analysis; AMNIOTIC-FLUID; EXTRACELLULAR VESICLES; ENDOTOXIN TOLERANCE; MESENCHYMAL CELLS; STEM-CELLS; POLARIZATION; EXOSOMES; SUPPRESSION; FEATURES; STATE;

D O I：

10.3390/ijms24032527

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In pregnancy, human amniotic fluid extracellular vesicles (HAF-EVs) exert anti-inflammatory effects on T cells and on monocytes, supporting their immunoregulatory roles. The specific mechanisms are still not completely defined. The aim of this study was to investigate the ability of HAF-EVs, isolated from pregnant women who underwent amniocentesis and purified by gradient ultracentrifugation, to affect inflammasome activation in the human monocytes. Proteomic studies revealed that HAF-EV samples expressed several immunoregulatory molecules as well as small amounts of endotoxin. Surprisingly, metagenomic analysis shows the presence of specific bacterial strain variants associated with HAF-EVs as potential sources of the endotoxin. Remarkably, we showed that a single treatment of THP-1 cells with HAF-EVs triggered inflammasome activation, whereas the same treatment followed by LPS and ATP sensitization prevented inflammasome activation, a pathway resembling monocyte refractories. A bioinformatics analysis of microbiota-HAF-EVs functional pathways confirmed the presence of enzymes for endotoxin biosynthesis as well as others associated with immunoregulatory functions. Overall, these data suggest that HAF-EVs could serve as a source of the isolation of a specific microbiota during early pregnancy. Moreover, HAF-EVs could act as a novel system to balance immune training and tolerance by modulating the inflammasome in monocytes or other cells.

引用

页数：18

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