Browse

Partial role of TLR4 as a receptor responding to damage-associated molecular pattern

Cited 33 time in Web of Science Cited 33 time in Scopus
Authors
Lee, Kyung-Mi; Seong, Seung-Yong
Issue Date
2009-06-30
Publisher
ELSEVIER SCIENCE BV
Citation
IMMUNOLOGY LETTERS; Vol.125 1; 31-39
Keywords
Toll-like receptorPAMPDAMPInflammationNF-κBNecrotic cellsDendritic cells
Abstract
Part of pathogen-associated molecular pattern (PAMP) and damage-associated molecular pattern (DAMP) activate antigen-presenting cells through Toll-like receptors (TLRs) to initiate immune responses. However, controversy remains if TLR4 mediates DAMP signaling due to the confounding effects of potential LPS contamination. To test if TLR4 functions as a true receptor for DAMP, we compared TLR4(pos)- and TLR4(neg)-responders in vitro and in vivo after stimulation with whole necrotic cell (NC) lysates. Using CHO reporter cells transfected with anti-TLR4-siRNAs, TLR4 was found to partially mediate NF-kappa B activation in response to NC lysates. TLR4(neg) DCs exhibited less I-A(b) expression and nitric oxide secretion than TLR4(pos) DCs upon NC stimulation and this defect was well correlated with diminished presentation of H-Y antigen by TLR4(neg) DCs to I-A(b)-restricted CD4(pos) Marilyn T cells in vitro. Similarly, TLR4(neg) DCs showed significantly less expression of I-A(b), CD80, CD86, and CD40 than TLR4(pos) DCs when NC lysates were injected into peritoneal cavity. Finally, delayed type hypersensitivity response to OVA was significantly decreased in TLR4(neg) mice when NCs were used as an adjuvant. Taken together, our data support the idea that part of the endogenous ligands presented by NCs could activate APCs thru TLR4 and contribute to the development of antigen-specific adaptive immunity. Therefore, endogenous DAMP ligands themselves, not contaminated LPS, activate TLR4 signaling leading to activation of professional antigen-presenting cells.
ISSN
0165-2478
Language
English
URI
https://hdl.handle.net/10371/76949
DOI
https://doi.org/10.1016/j.imlet.2009.05.006
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Microbiology (미생물학전공)Journal Papers (저널논문_미생물학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse