PMID- 34429858
OWN - NLM
STAT- MEDLINE
DCOM- 20220207
LR  - 20240403
IS  - 2001-3078 (Electronic)
IS  - 2001-3078 (Linking)
VI  - 10
IP  - 10
DP  - 2021 Aug
TI  - Parasite worm antigens instruct macrophages to release immunoregulatory 
      extracellular vesicles.
PG  - e12131
LID - 10.1002/jev2.12131 [doi]
LID - e12131
AB  - Emerging evidence suggests that immune cells not only communicate with each other 
      through cytokines, chemokines, and cell surface receptors, but also by releasing 
      small membranous structures known as extracellular vesicles (EVs). EVs carry a 
      variety of different molecules that can be taken up by recipient cells. Parasitic 
      worms are well known for their immunomodulatory properties, but whether they can 
      affect immune responses by altering EV-driven communication between host immune 
      cells remains unclear. Here we provide evidence that stimulation of bone 
      marrow-derived macrophages (BMDMs) with soluble products of Trichuris suis 
      (TSPs), leads to the release of EVs with anti-inflammatory properties. 
      Specifically, we found that EVs from TSP-pulsed BMDMs, but not those from 
      unstimulated BMDMs can suppress TNFalpha and IL-6 release in LPS-stimulated BMDMs and 
      BMDCs. However, no polarization toward M1 or M2 was observed in macrophages 
      exposed to EVs. Moreover, EVs enhanced reactive oxygen species (ROS) production 
      in the exposed BMDMs, which was associated with a deregulated redox homeostasis 
      as revealed by pathway analysis of transcriptomic data. Proteomic analysis 
      identified cytochrome p450 (CYP450) as a potential source of ROS in EVs from 
      TSP-pulsed BMDMs. Finally, pharmacological inhibition of CYP450 activity could 
      suppress ROS production in those BMDMs. In summary, we find that TSPs can 
      modulate immune responses not only via direct interactions but also indirectly by 
      eliciting the release of EVs from BMDMs that exert anti-inflammatory effects on 
      recipient cells.
CI  - (c) 2021 The Authors. Journal of Extracellular Vesicles published by Wiley 
      Periodicals, LLC on behalf of the International Society for Extracellular 
      Vesicles.
FAU - Zakeri, Amin
AU  - Zakeri A
AUID- ORCID: 0000-0001-7961-0634
AD  - Department of Clinical Medicine Aarhus University Aarhus Denmark.
FAU - Whitehead, Bradley J
AU  - Whitehead BJ
AD  - Department of Clinical Medicine Aarhus University Aarhus Denmark.
FAU - Stensballe, Allan
AU  - Stensballe A
AD  - Department of Medicine and Health Technology Aalborg University Aalborg Denmark.
FAU - de Korne, Clarize
AU  - de Korne C
AD  - Department of Parasitology Leiden University Medical Centre Leiden Netherlands.
AD  - Interventional Molecular Imaging laboratory Department of Radiology Leiden 
      University Medical Centre Leiden Netherlands.
FAU - Williams, Andrew R
AU  - Williams AR
AD  - Department of Veterinary and Animal Sciences Faculty of Health and Medical 
      Sciences University of Copenhagen Frederiksberg Denmark.
FAU - Everts, Bart
AU  - Everts B
AD  - Department of Parasitology Leiden University Medical Centre Leiden Netherlands.
FAU - Nejsum, Peter
AU  - Nejsum P
AD  - Department of Clinical Medicine Aarhus University Aarhus Denmark.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210816
PL  - United States
TA  - J Extracell Vesicles
JT  - Journal of extracellular vesicles
JID - 101610479
RN  - 0 (Antigens, Helminth)
RN  - 0 (Cytokines)
RN  - 0 (Proteome)
RN  - 0 (Reactive Oxygen Species)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Animals
MH  - Antigens, Helminth/*immunology/metabolism
MH  - Cell Cycle
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Cytokines/metabolism
MH  - Extracellular Vesicles/*immunology/*metabolism
MH  - Helminths/immunology/metabolism
MH  - Host-Parasite Interactions
MH  - Immunity
MH  - Immunomodulation
MH  - Macrophages/*immunology/*metabolism
MH  - Mice
MH  - Proteome/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Trichuriasis/*immunology
MH  - Trichuris/*immunology/metabolism
PMC - PMC8365858
OTO - NOTNLM
OT  - Trichuris suis soluble products
OT  - extracellular vesicles
OT  - inflammation
OT  - macrophages
OT  - reactive oxygen species
COIS- None.
EDAT- 2021/08/26 06:00
MHDA- 2022/02/08 06:00
PMCR- 2021/08/16
CRDT- 2021/08/25 06:23
PHST- 2021/05/15 00:00 [received]
PHST- 2021/07/14 00:00 [revised]
PHST- 2021/07/16 00:00 [accepted]
PHST- 2021/08/25 06:23 [entrez]
PHST- 2021/08/26 06:00 [pubmed]
PHST- 2022/02/08 06:00 [medline]
PHST- 2021/08/16 00:00 [pmc-release]
AID - JEV212131 [pii]
AID - 10.1002/jev2.12131 [doi]
PST - ppublish
SO  - J Extracell Vesicles. 2021 Aug;10(10):e12131. doi: 10.1002/jev2.12131. Epub 2021 
      Aug 16.