Characteristic and Functional Analysis of Toll-like Receptors (TLRs) in the lophotrocozoan, Crassostrea gigas, Reveals Ancient Origin of TLR-Mediated Innate Immunity
The evolution of TLR-mediated innate immunity is a fundamental question in immunology. Here, we report the characterization and functional analysis of four TLR members in the lophotrochozoans Crassostrea gigas (CgTLRs). All CgTLRs bear a conserved domain organization and have a close relationshi...
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| Format: | Online |
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Public Library of Science
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788107/ |
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pubmed-37881072013-10-04 Characteristic and Functional Analysis of Toll-like Receptors (TLRs) in the lophotrocozoan, Crassostrea gigas, Reveals Ancient Origin of TLR-Mediated Innate Immunity Zhang, Yang He, Xiaocui Yu, Feng Xiang, Zhiming Li, Jun Thorpe, Karen L. Yu, Ziniu Research Article The evolution of TLR-mediated innate immunity is a fundamental question in immunology. Here, we report the characterization and functional analysis of four TLR members in the lophotrochozoans Crassostrea gigas (CgTLRs). All CgTLRs bear a conserved domain organization and have a close relationship with TLRs in ancient non-vertebrate chordates. In HEK293 cells, every CgTLR could constitutively activate NF-κB responsive reporter, but none of the PAMPs tested could stimulate CgTLR-activated NF-κB induction. Subcellular localization showed that CgTLR members have similar and dual distribution on late endosomes and plasma membranes. Moreover, CgTLRs and CgMyD88 mRNA show a consistent response to multiple PAMP challenges in oyster hemocytes. As CgTLR-mediated NF-κB activation is dependent on CgMyD88, we designed a blocking peptide for CgTLR signaling that would inhibit CgTLR-CgMyD88 dependent NF-κB activation. This was used to demonstrate that a Vibrio parahaemolyticus infection-induced enhancement of degranulation and increase of cytokines TNF mRNA in hemocytes, could be inhibited by blocking CgTLR signaling. In summary, our study characterized the primitive TLRs in the lophotrocozoan C . gigas and demonstrated a fundamental role of TLR signaling in infection-induced hemocyte activation. This provides further evidence for an ancient origin of TLR-mediated innate immunity. Public Library of Science 2013-10-01 /pmc/articles/PMC3788107/ /pubmed/24098508 http://dx.doi.org/10.1371/journal.pone.0076464 Text en © 2013 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Zhang, Yang He, Xiaocui Yu, Feng Xiang, Zhiming Li, Jun Thorpe, Karen L. Yu, Ziniu |
| spellingShingle |
Zhang, Yang He, Xiaocui Yu, Feng Xiang, Zhiming Li, Jun Thorpe, Karen L. Yu, Ziniu Characteristic and Functional Analysis of Toll-like Receptors (TLRs) in the lophotrocozoan, Crassostrea gigas, Reveals Ancient Origin of TLR-Mediated Innate Immunity |
| author_facet |
Zhang, Yang He, Xiaocui Yu, Feng Xiang, Zhiming Li, Jun Thorpe, Karen L. Yu, Ziniu |
| author_sort |
Zhang, Yang |
| title |
Characteristic and Functional Analysis of Toll-like Receptors (TLRs) in the lophotrocozoan, Crassostrea
gigas, Reveals Ancient Origin of TLR-Mediated Innate Immunity |
| title_short |
Characteristic and Functional Analysis of Toll-like Receptors (TLRs) in the lophotrocozoan, Crassostrea
gigas, Reveals Ancient Origin of TLR-Mediated Innate Immunity |
| title_full |
Characteristic and Functional Analysis of Toll-like Receptors (TLRs) in the lophotrocozoan, Crassostrea
gigas, Reveals Ancient Origin of TLR-Mediated Innate Immunity |
| title_fullStr |
Characteristic and Functional Analysis of Toll-like Receptors (TLRs) in the lophotrocozoan, Crassostrea
gigas, Reveals Ancient Origin of TLR-Mediated Innate Immunity |
| title_full_unstemmed |
Characteristic and Functional Analysis of Toll-like Receptors (TLRs) in the lophotrocozoan, Crassostrea
gigas, Reveals Ancient Origin of TLR-Mediated Innate Immunity |
| title_sort |
characteristic and functional analysis of toll-like receptors (tlrs) in the lophotrocozoan, crassostrea
gigas, reveals ancient origin of tlr-mediated innate immunity |
| description |
The evolution of TLR-mediated innate immunity is a fundamental question in immunology. Here, we report the characterization and functional analysis of four TLR members in the lophotrochozoans
Crassostrea
gigas
(CgTLRs). All CgTLRs bear a conserved domain organization and have a close relationship with TLRs in ancient non-vertebrate chordates. In HEK293 cells, every CgTLR could constitutively activate NF-κB responsive reporter, but none of the PAMPs tested could stimulate CgTLR-activated NF-κB induction. Subcellular localization showed that CgTLR members have similar and dual distribution on late endosomes and plasma membranes. Moreover, CgTLRs and CgMyD88 mRNA show a consistent response to multiple PAMP challenges in oyster hemocytes. As CgTLR-mediated NF-κB activation is dependent on CgMyD88, we designed a blocking peptide for CgTLR signaling that would inhibit CgTLR-CgMyD88 dependent NF-κB activation. This was used to demonstrate that a Vibrio parahaemolyticus infection-induced enhancement of degranulation and increase of cytokines TNF mRNA in hemocytes, could be inhibited by blocking CgTLR signaling. In summary, our study characterized the primitive TLRs in the lophotrocozoan
C
. gigas
and demonstrated a fundamental role of TLR signaling in infection-induced hemocyte activation. This provides further evidence for an ancient origin of TLR-mediated innate immunity. |
| publisher |
Public Library of Science |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788107/ |
| _version_ |
1612015582080663552 |