PMID- 30087675
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 9
DP  - 2018
TI  - Extracellular Vesicles Secreted by Neospora caninum Are Recognized by Toll-Like 
      Receptor 2 and Modulate Host Cell Innate Immunity Through the MAPK Signaling 
      Pathway.
PG  - 1633
LID - 10.3389/fimmu.2018.01633 [doi]
LID - 1633
AB  - Neospora caninum is an obligate intracellular parasite, which causes significant 
      economic losses in the cattle industry. However, the immune mechanism of the 
      parasite-host interaction is not yet fully understood. Extracellular vesicles 
      (EVs) have emerged as a ubiquitous mechanism by which almost all cells, 
      especially immune and tumor cells, participate in intercellular communications. 
      Although studies have indicated that EVs secreted by Toxoplasma gondii or 
      Trypanosoma brucei promote exchanges of biological molecules important for the 
      host-parasite interplay, however, EVs and their biological activities in N. 
      caninum is not clear. Here, we used multiple methods, including electron 
      microscopy, nanoparticle tracking analysis, RT-PCR, immunofluorescence, western 
      blot, proteomics, and cytokine analyses, to examine the properties of N. caninum 
      EVs. We found that N. caninum produced EVs that are similar to mammalian 
      exosomes, which generally range from 30 to 150 nm in diameter. It was shown that 
      N. caninum EVs could remarkably increase the production of pro-inflammatory 
      cytokines IL-12p40, TNF-alpha, IL-1beta, IL-6, and IFN-gamma by wild-type (WT) mouse bone 
      marrow-derived macrophages (BMDMs) whereas the secretion of IL-12p40, TNF-alpha, and 
      IFN-gamma was very strongly downregulated in TLR2(-/-) mouse BMDMs. The levels of 
      IL-6 were not affected, but the secretion of IL-10 was upregulated. We found that 
      the phosphorylation levels of P38, ERK, and JNK were significantly reduced in the 
      TLR2(-/-) cells compared with those in WT mouse BMDMs and that treatment with 
      chemical inhibiters of P38, ERK, and JNK resulted in upregulation of IL-6, 
      IL-12p40, and IL-10 production. Together, these results demonstrated that N. 
      caninum EVs could be rapidly internalized to deliver proteins to the host cells 
      and modulate the host cell immune responses through MAPK signaling pathway in a 
      TLR2-dependent manner. Our study is the first to reveal potential roles for N. 
      caninum EVs in host communication and immune response in parasite-host 
      interactions.
FAU - Li, Shan
AU  - Li S
AD  - College of Veterinary Medicine, Jilin University, Changchun, China.
FAU - Gong, Pengtao
AU  - Gong P
AD  - College of Veterinary Medicine, Jilin University, Changchun, China.
FAU - Tai, Lixin
AU  - Tai L
AD  - College of Veterinary Medicine, Jilin University, Changchun, China.
FAU - Li, Xin
AU  - Li X
AD  - College of Veterinary Medicine, Jilin University, Changchun, China.
FAU - Wang, Xiaocen
AU  - Wang X
AD  - College of Veterinary Medicine, Jilin University, Changchun, China.
FAU - Zhao, Chunyan
AU  - Zhao C
AD  - College of Veterinary Medicine, Jilin University, Changchun, China.
FAU - Zhang, Xu
AU  - Zhang X
AD  - College of Veterinary Medicine, Jilin University, Changchun, China.
FAU - Yang, Zhengtao
AU  - Yang Z
AD  - College of Veterinary Medicine, Jilin University, Changchun, China.
FAU - Yang, Ju
AU  - Yang J
AD  - College of Veterinary Medicine, Jilin University, Changchun, China.
FAU - Li, Jianhua
AU  - Li J
AD  - College of Veterinary Medicine, Jilin University, Changchun, China.
FAU - Zhang, Xichen
AU  - Zhang X
AD  - College of Veterinary Medicine, Jilin University, Changchun, China.
LA  - eng
PT  - Journal Article
DEP - 20180724
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC6066505
OTO - NOTNLM
OT  - MAPK
OT  - Neospora caninum
OT  - extracellular vesicles
OT  - innate immunity
OT  - toll-like receptor 2
EDAT- 2018/08/09 06:00
MHDA- 2018/08/09 06:01
PMCR- 2018/01/01
CRDT- 2018/08/09 06:00
PHST- 2018/03/22 00:00 [received]
PHST- 2018/07/02 00:00 [accepted]
PHST- 2018/08/09 06:00 [entrez]
PHST- 2018/08/09 06:00 [pubmed]
PHST- 2018/08/09 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2018.01633 [doi]
PST - epublish
SO  - Front Immunol. 2018 Jul 24;9:1633. doi: 10.3389/fimmu.2018.01633. eCollection 
      2018.