Interspecies communication between plant and mouse gut host cells through edible plant derived exosome-like nanoparticles.
METHODS
Exosomes, small vesicles participating in intercellular communication, have been extensively studied recently; however, the role of edible plant derived exosomes in interspecies communication has not been investigated. Here, we investigate the biological effects of edible plant derived exosome-like nanoparticles (EPDENs) on mammalian cells.


RESULTS
In this study, exosome-like nanoparticles from four edible plants were isolated and characterized. We show that these EPDENs contain proteins, lipids, and microRNA. EPDENs are taken up by intestinal macrophages and stem cells. The results generated from EPDEN-transfected macrophages indicate that ginger EPDENs preferentially induce the expression of the antioxidation gene, heme oxygenase-1 and the anti-inflammatory cytokine, IL-10; whereas grapefruit, ginger, and carrot EPDENs promote activation of nuclear factor like (erythroid-derived 2). Furthermore, analysis of the intestines of canonical Wnt-reporter mice, i.e. B6.Cg-Tg(BAT-lacZ)3Picc/J mice, revealed that the numbers of β-galactosidase(+) (β-Gal) intestinal crypts are increased, suggesting that EPDEN treatment of mice leads to Wnt-mediated activation of the TCF4 transcription machinery in the crypts.


CONCLUSIONS
The data suggest a role for EPDEN-mediated interspecies communication by inducing expression of genes for anti-inflammation cytokines, antioxidation, and activation of Wnt signaling, which are crucial for maintaining intestinal homeostasis.
Department of Microbiology & Immunology, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA.
Jingyao
J
Mu
Xiaoying
X
Zhuang
Qilong
Q
Wang
Hong
H
Jiang
Zhong-Bin
ZB
Deng
Baomei
B
Wang
Lifeng
L
Zhang
Sham
S
Kakar
Yan
Y
Jun
Donald
D
Miller
Huang-Ge
HG
Zhang
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication; D045744:Cell Line, Tumor; D032083:Citrus paradisi / Q000737:chemistry; D018552:Daucus carota / Q000737:chemistry; D055354:Exosomes / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000166:cytology / Q000378:metabolism*; D020939:Zingiber officinale / Q000737:chemistry; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000201:enzymology; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010945:Plants, Edible / Q000737:chemistry*; D000073940:Transcription Factor 4; D027843:Vitis / Q000737:chemistry; D060449:Wnt Signaling Pathway; D001616:beta-Galactosidase / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C090743:Tcf4 protein, mouse; D000073940:Transcription Factor 4; D016753:Interleukin-10; D051547:Heme Oxygenase-1; D001616:beta-Galactosidase
Anti-inflammation; Antioxidation; Edible plant exosomes; Intestinal macrophages; Nrf2